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‣ Progress and controversies in developing cancer vaccines

Slingluff, Craig L; Speiser, Daniel E
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 29/04/2005 Português
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Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2) and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

‣ Dendritic cell-based therapeutic cancer vaccines: what we have and what we need

Kalinski, Pawel; Urban, Julie; Narang, Rahul; Berk, Erik; Wieckowski, Ewa; Muthuswamy, Ravikumar
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/2009 Português
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Therapeutic cancer vaccines rely on the immune system to eliminate tumor cells. In contrast to chemotherapy or passive (adoptive) immunotherapies with antibodies or ex vivo-expanded T cells, therapeutic vaccines do not have a direct anti-tumor activity, but aim to reset patients’ immune systems to achieve this goal. Recent identification of effective ways of enhancing immunogenicity of tumor-associated antigens, including the use of dendritic cells and other potent vectors of cancer vaccines, provide effective tools to induce high numbers of circulating tumor-specific T cells. However, despite indications that some of the new cancer vaccines may be able to delay tumor recurrence or prolong the survival of cancer patients, their ability to induce cancer regression remains low. Recent reports help to identify and prospectively remove the remaining obstacles towards effective therapeutic vaccination of cancer patients. They indicate that the successful induction of tumor-specific T cells by cancer vaccines is not necessarily associated with the induction of functional cytotoxic T lymphocytes, and that current cancer vaccines may promote undesirable expansion of Treg cells. Furthermore, recent studies also identify the tools to counteract such phenomena...

‣ Enhancing cellular cancer vaccines

Cohen, Edward P; Chopra, Amla; O-Sullivan, InSug; Kim, Tae Sung
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/05/2009 Português
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Various strategies have been used to generate cellular cancer vaccines with the expectation that they will become an effective part of the overall management of cancer patients. However, with few notable exceptions, immunization has not resulted in significant long-term therapeutic benefits. Tumor growth has continued and patient survival has been at best only modestly prolonged. One possible explanation is that as only a small proportion of the constituents of malignant cells are ‘tumor specific’ and the vast majority are the products of nonantigenic, normal ‘housekeeping’ genes, the immune response in patients immunized with cellular cancer vaccines is not sufficient to result in tumor rejection. Here, we review and characterize various types of cellular cancer vaccines. In addition, in a mouse breast cancer model system, we describe a unique strategy designed to enrich cellular vaccines for cells that induce tumor immunity. Numerous advantages and disadvantages of cancer immunotherapy with cellular vaccines are also presented.

‣ Sperm fibrous sheath proteins: a potential new class of target antigens for use in human therapeutic cancer vaccines

Chiriva-Internati, Maurizio; Cobos, Everardo; Da Silva, Diane M.; Kast, W. Martin
Fonte: Academy of Cancer Immunology Publicador: Academy of Cancer Immunology
Tipo: Artigo de Revista Científica
Publicado em 24/04/2008 Português
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Cancer vaccines have been demonstrated to be a promising strategy for treating human neoplastic disease, but one of the limitations of these vaccines remains the paucity of target antigens to which to direct an effective immune response. We hypothesize that sperm fibrous sheath proteins may be a new class of useful antigens for developing successful cancer vaccines. This hypothesis is supported by the expression of two sperm fibrous sheath proteins, called sperm protein 17 and calcium-binding tyrosine-phosphorylation regulated protein, in tumors of unrelated histological origin and their capability to induce T cell-based immune responses.

‣ Translating Tumor Antigens into Cancer Vaccines ▿

Buonaguro, Luigi; Petrizzo, Annacarmen; Tornesello, Maria Lina; Buonaguro, Franco M.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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Vaccines represent a strategic successful tool used to prevent or contain diseases with high morbidity and/or mortality. However, while vaccines have proven to be effective in combating pathogenic microorganisms, based on the immune recognition of these foreign antigens, vaccines aimed at inducing effective antitumor activity are still unsatisfactory. Nevertheless, the effectiveness of the two licensed cancer-preventive vaccines targeting tumor-associated viral agents (anti-HBV [hepatitis B virus], to prevent HBV-associated hepatocellular carcinoma, and anti-HPV [human papillomavirus], to prevent HPV-associated cervical carcinoma), along with the recent FDA approval of sipuleucel-T (for the therapeutic treatment of prostate cancer), represents a significant advancement in the field of cancer vaccines and a boost for new studies in the field. Specific active immunotherapies based on anticancer vaccines represent, indeed, a field in continuous evolution and expansion. Significant improvements may result from the selection of the appropriate tumor-specific target antigen (to overcome the peripheral immune tolerance) and/or the development of immunization strategies effective at inducing a protective immune response. This review aims to describe the vast spectrum of tumor antigens and strategies to develop cancer vaccines.

‣ Cancer vaccines

Liu, Margaret A.
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em 12/10/2011 Português
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While vaccines are primarily thought of in terms of their use for prevention of infectious diseases, they can potentially be used to prevent or treat cancer. This manuscript explores the rationale for vaccines and immunotherapies for cancer from both the scientific and the global needs perspectives. Pathogens that are aetiologic agents of certain cancers provide perhaps the most obvious successful examples of the prophylactic utility of vaccines (such as the hepatitis B vaccine) to prevent not just the infectious disease (hepatitis), but the potential subsequent cancer (hepatocellular carcinoma). The use of monoclonal antibodies illustrates the effectiveness of the immune system for cancer therapy. In addition, the increased understanding of the role and mechanisms of the immune system in the processes of immune surveillance, as well as of its failure during immunosuppression, have yielded better insights into how to design cancer vaccines and immunotherapies. Examples of targets for cancer vaccines will be discussed, as will the challenges and few successes in this arena.

‣ Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression

Madan, Ravi A.; Gulley, James L.; Fojo, Tito; Dahut, William L.
Fonte: AlphaMed Press Publicador: AlphaMed Press
Tipo: Artigo de Revista Científica
Português
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The article examines the potential reasons for the delayed clinical benefits seen with therapeutic cancer vaccines and the broader implications for evolving treatment paradigms.

‣ Update on Prostate Cancer Vaccines

Drake, Charles G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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The recent FDA approval of Sipuleucel-T (Dendreon, Seattle WA) for the treatment of men with asymptomatic or minimally symptomatic castrate resistant prostate cancer was a landmark in cancer immunotherapy, making this the first cancer “vaccine” approved for use in a treatment setting. This approval has led to renewed interest in cancer vaccines, and to the recognition that prostate cancer represents an immunologically sensitive disease. At the current time, several vaccine approaches are under clinical investigation. These include viral vectors, antigen-loaded dendritic cells, and DNA vaccines. Each approach has its own set of advantages and disadvantages. This review will introduce the basic technology underlying these different vaccines, and briefly discuss completed and ongoing clinical trials. As a great number of prostate cancer vaccines have been investigated in both preclinical and clinical settings, we will focus primarily on vaccines that are currently in clinical trials, as ascertained by a recent inquiry of the clinical trials database www.clinicaltrials.gov.

‣ Cancer vaccines: current directions and perspectives in prostate cancer

Mohebtash, Mahsa; Gulley, James L.; Madan, Ravi A.; Arlen, Philip M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/2009 Português
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Numerous ongoing studies are investigating the use of cancer vaccines as a potential therapeutic modality for various tumor types. The efficacy of cancer vaccines has improved thanks to advances in the characterization of tumor-associated antigens, the development of better vaccine delivery systems, and the combination of vaccines with cytokines and other immunostimulants to enhance immune responses. Although cancer vaccines are being studied in many different tumor types, several characteristics of prostate cancer make it an ideal target for immunotherapy. Prostate cancer’s relative indolence allows sufficient time to generate immune responses, which usually take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal tissue. This review focuses on promising new approaches for combining vaccines with other therapeutic strategies, as well as novel perspectives in the treatment of prostate cancer.

‣ Cancer vaccines: Looking to the future

Yaddanapudi, Kavitha; Mitchell, Robert A.; Eaton, John W.
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Português
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These are exciting times for the field of cancer immunotherapy. Although the clinical efficacy of monoclonal antibodies has been demonstrated since the early 1990s, the therapeutic profile of other immunotherapeutic approaches—especially vaccines—has not yet been formally clarified. However, the recent success of several immunotherapeutic regimens in cancer patients has boosted the development of this treatment modality. These achievements stemmed from recent scientific advances demonstrating the tolerogenic nature of cancer and the fundamental role of the tumor immune microenvironment in the suppression of antitumor immunity. New immunotherapeutic strategies against cancer attempt to promote protective antitumor immunity while disrupting the immunoregulatory circuits that contribute to tumor tolerance. Cancer vaccines differ from other anticancer immunotherapeutics in that they initiate the dynamic process of activating the immune system so as to successfully re-establish a state of equilibrium between tumor cells and the host. This article reviews recent clinical trials involving several different cancer vaccines and describes some of the most promising immunotherapeutic approaches that harness antitumor T-cell responses. In addition...

‣ Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

Weir, Genevieve M.; Liwski, Robert S.; Mansour, Marc
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 05/08/2011 Português
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Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

‣ Emerging Cancer Vaccines: The Promise of Genetic Vectors

Aurisicchio, Luigi; Ciliberto, Gennaro
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 22/09/2011 Português
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Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines...

‣ Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

Rodriguez, Pedro C; Sanchez, Belinda
Fonte: Bentham Science Publishers Publicador: Bentham Science Publishers
Tipo: Artigo de Revista Científica
Português
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This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system...

‣ Generation of more effective cancer vaccines

Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Kalli, Francesca; Zanetti, Maurizio; Filaci, Gilberto
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Português
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47.418228%
Cancer vaccines represent a promising therapeutic approach for which prime time is imminent. However, clinical efficacy must be improved in order for cancer vaccines to become a valid alternative or complement to traditional cancer treatments. Considerable efforts have been undertaken so far to better understand the fundamental requirements for clinically-effective cancer vaccines. Recent data emphasize that important requirements, among others, are (1) the use of multi-epitope immunogens, possibly deriving from different tumor antigens; (2) the selection of effective adjuvants; (3) the association of cancer vaccines with agents able to counteract the regulatory milieu present in the tumor microenvironment; and (4) the need to choose the definitive formulation and regimen of a vaccine after accurate preliminary tests comparing different antigen formulations. The first requirement deals with issues related to HLA restriction of tumor antigen presentation, as well as usefulness of tumor antigen spreading and counteraction of immune escape phenomena, linked to tumor antigen down-modulation, for an effective anti-cancer immune response. The second point underscores the necessity of optimal activation of innate immunity to achieve an efficient adaptive anti-cancer immune response. The third point focuses on the importance to inhibit subsets of regulatory cells. The last requirement stresses the concept that the regimen and formulation of the vaccine impacts profoundly on cancer vaccine efficacy. A new generation of cancer vaccines...

‣ Anti-Cancer Vaccines — A One-Hit Wonder?

Liu, Justin K.H.
Fonte: YJBM Publicador: YJBM
Tipo: Artigo de Revista Científica
Publicado em 12/12/2014 Português
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Immunization against common bacterial and viral diseases has helped prevent millions of deaths worldwide. More recently, the concept of vaccination has been developed into a potentially novel strategy to treat and prevent cancer formation, progression, and spread. Over the past few years, a handful of anti-cancer vaccines have been licensed and approved for use in clinical practice, thus providing a breakthrough in the field. However, the path has not always been easy, with many hurdles that have had to be overcome in order to reach this point. Nevertheless, with more anti-cancer vaccines currently in development, there is still hope that they can eventually become routine tools used in the treatment and prevention of cancer in the future. This review will discuss in detail both types of anti-cancer vaccine presently used in clinical practice — therapeutic and preventive — before considering some of the more promising anti-cancer vaccines that are currently in development. Finally, the issue of side effects and the debate surrounding the overall cost-effectiveness of anti-cancer vaccines will be examined.

‣ Potential Benefits of Second-Generation Human Papillomavirus Vaccines

Kiatpongsan, Sorapop; Campos, Nicole Gastineau; Kim, Jane Jooyun
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Background: Current prophylactic vaccines against human papillomavirus (HPV) target two oncogenic types (16 and 18) that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58). Methods: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda) was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer) and vaccine properties (i.e., cross-protection against non-targeted HPV types), compared against currently-available vaccines. Results: Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda...

‣ Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines

Ali, Omar Abdel-Rahman; Doherty, Edward; Mooney, David J.; Emerich, Dwaine
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Português
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Cancer vaccines are typically formulated for bolus injection and often produce short-lived immunostimulation resulting in poor temporal control over immune cell activation and weak oncolytic activity. One means of overcoming these limitations utilizes immunologically active biomaterial constructs. We previously reported that antigen-laden, macroporous PLG scaffolds induce potent dendritic cell (DC) and cytotoxic T-lymphocyte (CTL) responses via the controlled signaling of inflammatory cytokines, antigen and toll-like receptor agonists. In this study, we describe the kinetics of these responses and illustrate their fundamental relationship to potent tumor rejection when implanted subcutaneously in a mouse B16 model of melanoma. By explanting scaffolds from mice at times ranging from 1–7 d, a seamless relationship was observed between the production of controlled CTL responses, tumor growth and long-term survival in both prophylactic and therapeutic models. Scaffolds must be implanted for > 7 d to augment CTL responses via the prolonged presentation of tumor antigen, and the benefits included a notable regression of established tumors. Host DC infiltration into the porous material persisted for 12 days (peaking at day 5 ~1.4 x 106 cells)...

‣ Dendritic Cell Cancer Vaccines: From the Bench to the Bedside

Katz, Tamar; Avivi, Irit; Benyamini, Noam; Rosenblatt, Jacalyn; Avigan, David
Fonte: Rambam Health Care Campus Publicador: Rambam Health Care Campus
Tipo: Artigo de Revista Científica
Português
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The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both “passive” (e.g. strategies relying on the administration of specific T cells) and “active” vaccines (e.g. peptide-directed or whole-cell vaccines) have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines) are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target “immunosuppressive checkpoints” (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination.

‣ Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors

Kleponis, Jennifer; Skelton, Richard; Zheng, Lei
Fonte: Chinese Anti-Cancer Association Publicador: Chinese Anti-Cancer Association
Tipo: Artigo de Revista Científica
Publicado em /09/2015 Português
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Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

‣ Improving cellular cancer vaccines

Petr Lokhov
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
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Immunization with cancer cells is of great demand in anti-cancer therapy. However, current cellular vaccines are inefficient and there are questions regarding their overall safety. We report a simple and straightforward approach for improving of cellular cancer vaccines. Through treatment of cancer cell cultures with purified protease, it is possible to make preparations of cell-surface antigens that are free of intracellular content and contain two orders-of-magnitude less protein than the whole lysate of an equivalent number of cancer cells. Despite this difference in total protein content, protease-generated preparations stimulate anti-cancer responses from immune cells better those stimulated with cancer cells themselves. The composition of collected cell-surface antigens, prior to vaccination, can be directly compared with antigenic profile of target cancer cells by the proteomic footprinting. Any contaminates (cell parasites, viruses, toxins, prions, etc.) are easily separated from antigens by means of ultrafiltration. Thus, current cellular vaccines may be improved by replacing whole cancer cells with their isolated cell-surface antigens. Vaccines prepared in this manner are potentially more qualified, purer, and safer.