Development Of Antitumor Vaccines Research Articles

ITTCA-MVL: A multi-view learning model based on physicochemical information and sequence statistical information for tumor T cell antigens identification

Immunotherapy is an emerging treatment method aimed at activating the human immune system and relying on its own immune function to kill cancer cells and tumor tissues. It has the advantages of wide applicability and minimal side effects. Effective identification of tumor T cell antigens (TTCAs) will help researchers understand their functions and mechanisms and carry out research on anti-tumor vaccine development. Considering that using biological experimental technology to identify TTCAs can be costly and time-consuming, it is necessary to develop a robust bioinformatics computing tool. At present, different machine learning models have been proposed for identifying TTCAs, but there is still room for further improvement in their performance. To establish a TTCA predictor with better prediction performance, we propose a prediction model called iTTCA-MVL in this paper. We extracted three sets of features from the views of physicochemical information and sequence statistics, namely the distribution descriptor of composition, transition, and distribution (CTDD), TF-IDF, and LSA topic. Then, we used least squares support vector machines (LSSVMs) as submodels and Hilbert‒Schmidt independence criteria (HSIC) as constraints to establish an independent and complementary multi-view learning model. The prediction accuracy of iTTCA-MVL on the independent test set is 0.873, and Matthew's correlation coefficient is 0.747, which is significantly better than those of existing methods. Therefore, iTTCA-MVL is an excellent prediction tool that researchers can use to accurately identify TTCAs.

Abstract LB168: Efficacy analysis of the DeepNeo neoantigen prediction tool for antitumor vaccine development

Abstract Antitumor peptide vaccine is an alternative and attractive way to eradicate tumors by the aid of host immune system. The current peptide vaccine development is hampered by several hurdles. These include heterogeneity of tumor cells, applicable in vivo stability of peptides, and others. One of the major obstacles is the precise prediction of cancer antigen, which can be loaded efficiently onto antigen presenting cells. We present here a neoantigen prediction algorithm DeepNeo comprised of DeepNeo-MHC and DeepNeo-TCR, which calculates the antigenicity of neoantigen based on the MHC binding and TCR activation potential. We examined the efficacy of DeepNeo using ELISPOT and two allogenic mouse tumor models. By treating the combination of long peptides targeting MC38 colon or B16F10 melanoma cell lines, we have shown the DeepNeo effectively determines neoantigens for the development of antitumor peptide vaccine. Analysis of tumor-infiltrated lymphocytes (TIL) supported our results. Undergoing study using patient-derived xenograft model treated with autologous, trained PBMC with personalized peptide vaccine will be discussed further. Citation Format: Eun Ji Lee, Min Ji Park, Soo Jin Kim, Seung-Jae Noh, Inkyung Shin, Jeong Yeon Kim, Incheol Shin, Jung Kyoon Choi, Dae-Yeon Cho, Suhwan Chang. Efficacy analysis of the DeepNeo neoantigen prediction tool for antitumor vaccine development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB168.

Extracellular vesicles in vaccine development and therapeutic approaches for viral diseases

Extracellular vesicles (EVs) are lipid bilayer nanovesicles generated by almost all living cells which possess various size ranges depending on producer cells and biogenesis mechanisms. Several EV markers were determined including tetraspanins (e.g., CD9, CD63 and CD81), heat shock proteins (HSP70 and HSP90), some 14–3–3 proteins (a family of conserved regulatory molecules), major histocompatibility complex molecules (MHC-I/-II), and enzymes (Glyceraldehyde 3-phosphate dehydrogenase and enolase-1). EVs are known as an abundant source of antigens and immune molecules that can be used for vaccine development in human and animals. EV-based immunization could significantly activate immune responses in different infections such as Porcine reproductive and respiratory syndrome virus (PRRSV), Lymphocytic choriomeningitis virus (LCMV), Marek’s disease virus (MDV), and SARS-CoV-2 infections. The engineered and modified EVs showed a promising potential in development of anti-tumor vaccines and therapeutics, protection against parasitic diseases (e.g., Eimeria, and Plasmodium yoelii) and viral diseases (e.g., COVID-19), and improvement of biomarkers. Also, EVs possess a crucial role in antigen presentation in vivo. In this review, we describe the roles of EVs in vaccine development and therapeutic approaches for viral diseases.

Peptide antitumor vaccines targeting HER2/neu

Antitumor vaccines are aimed at correcting cellular immunity by overcoming immunological tolerance with eluding surveillance due to the specific presentation of tumor-associated or tumor-specific antigens to immunocompetent cells.The purpose of this review was to study modern strategies for the development of antitumor vaccines containing epitopes of HER2/neu receptors acting as tumor-associated antigens. Approaches to the creation of such vaccines are classified by targeting the T-cell link or B-cells by the choice and length of the epitopes used or by the use of specific adjuvants.The review provides information on this topic, obtained from more than 50 publications of the last 20 years, found in the most significant sources of citation. The text is categorized for the convenience of perception by scientists of different specialties and is completed with a brief conclusion with an emphasis on development prospects. The results of clinical studies of vaccines with an analysis of the immunological features of the results of immunotherapy, mainly breast cancer with HER2/neu expression, are considered. Vaccines targeting different histocompatibility complexes are compared. The review traces the evolution of vaccine preparations from the simplest containing short peptide sequences to complex combined systems, including viral vectors. Attention is paid to various methodological approaches used in the development of such drugs: from computer design and phage display in experiments in vitro/in vivo. The emphasis is placed on the problem of a personalized approach to vaccination of an oncological patient associated with a mutation process occurring inside tumors and leading to the appearance of unique tumor-associated antigens. The participation of complement system components in antibody-mediated lysis of tumor cells induced by the presented vaccines is discussed.Thus, the review introduces readers to the existing directions of creating immune drugs designed to suppress the development of the tumor process by activating the body’s own immune forces and the prospect of their development.

Functional Role of Glycosphingolipids in Cancer.

Glycosphingolipids (GSLs) are ubiquitous components on animal cell membranes, and exposed on the outer surface. Various studies have demonstrated that they play key roles in cell proliferation, adhesion, motility and differentiation. Usually, the specific types of GSLs are expressed more highly in tumors than in normal tissues, which are known as tumorassociated antigens. It has been revealed that most tumor cells show altered GSLs patterns on their surface, abnormal GSLs signaling and biosynthesis, which together play a major role in tumor development. Tumor-associated GSL antigens have been used in the development of antitumor vaccines. There is no doubt that GSLs play a crucial role in tumor progression and would be a promising target for cancer treatment.

A Novel Dendritic Cell-Based Vaccination Protocol to Stimulate Immunosurveillance of Aggressive Cancers.

A major challenge in the development of a successful tumor vaccination is to break immune tolerance and to sensitize efficiently the immune system toward relevant tumor antigens, thus enabling T-cell-mediated antitumor responses in vivo. Dendritic cell (DC)-based immunotherapy shows the advantage to induce an adaptive immune response against the tumor, with the potential to generate a long-lasting immunological memory able to prevent further relapses and hopefully metastasis. Recently different preclinical studies highlighted the golden opportunity to exploit the features of immunogenic cell death (ICD) to generate ex vivo a highly immunogenic tumor cell lysate as potent antigen formulation for improved DC-based vaccine against aggressive cancers. This chapter focuses on the methods to obtain tumor lysates from cells undergoing ICD to be used for DC pulsing and to test the functionality of the generated DCs for antitumor vaccine development.

Abstract B14: Neoantigen burden associates with chemoresponse in muscle-invasive bladder cancer patients receiving neoadjuvant chemotherapy

Abstract Background: The basis of response to chemotherapy is incompletely characterized. The immune system is increasingly recognized as both a key player in cancer control and as druggable target. We hypothesized that the immune system impacts pathologic response in patients undergoing cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive (≥pT2) bladder cancer though neoantigens present in tumors. Methods: Whole exome sequencing (WES) was performed on tumor DNA from patients in two independent cohorts who underwent cisplatin-based NAC. Pathologic response was defined in the cystectomy specimen. The Memorial Sloan Kettering/Dana Farber Cancer institute (MSKCC/DFCI) cohort (n=50; 25 ≤ pTis responders) and Philadelphia cohorts (n=48; 20 ≤ pTis responders) were treated with gemcitabine/ cisplatin or methotrexate/ vinblastine/ doxorubicin/ cisplatin. Mutation analysis was performed using standard analytical pipelines. Macrohistocompatibility complex (MHC)-restricted neoantigens were identified with netMHCpan and PolySolver. Wilcoxon rank sum test was used to test for significance and all tests were two-sided. Results: In both cohorts, mutation rate associated with pathologic response (p<0.01 and p<0.001 in Philadelphia and MSKCC/DFCI cohorts, respectively). In the MSKCC/DFCI cohort, the median predicted high affinity (Kd<500 nM) neoantigen count was 311 versus 154 for responding and nonresponding tumors, respectively (p=0.002). For the Philadelphia cohort, the median neoantigen count was 439 versus 218 for responding and nonresponding tumors, respectively (p=8.2 x 10-7). The relationship between neoantigen density and response maintained significance independent of the definition of response (pT0, ≤ pTis, ≤ pT1) and independent of the neoantigen Kd (500 nM, 100 nM, 50 nM) in both cohorts and when cohorts were combined. Conclusions: Mutational load and neoantigen burden correlate strongly with pathologic response to NAC. Chemotherapy may therefore exert tumor cell autonomous effects through apoptotic mechanisms and a tumor cell extrinsic effect by alerting the immune system via neoantigen presentation on dying cells. Mutation rate is likely directly correlated to neoantigen burden and both may impact patient selection for chemotherapy alone or in combination with immunotherapy agents, and development of antitumor vaccines. Experiments are underway to more directly characterize the impact of the immune system in the response to chemotherapy. Citation Format: Philip H. Abbosh, David Liu, Michael H. Johnson, Wafik S. El-Deiry, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen. Neoantigen burden associates with chemoresponse in muscle-invasive bladder cancer patients receiving neoadjuvant chemotherapy. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B14.

Polyguanine-conjugated antigens target scavenger receptors in dendritic cells and induce antitumor immunity against melanoma

Abstract We have developed a vaccine design involving the conjugation of polyguanine (Poly(dG)) to protein or peptide antigens for the specific targeting of scavenger receptors in dendritic cells with intrinsic adjuvant capabilities. We have shown that Poly(dG) conjugation to ovalbumin generates stable particle conjugates (Poly(dG)-OVA) that induce greater T cell (helper, cytotoxic, and memory) and antibody responses. In this study, we show that Poly(dG)-OVA treatment of DCs in vitro induces greater antigen internalization and expression of activation markers CD86, MHC II, and CCR7. In vivo, intradermal injection of Poly(dG)-OVA resulted in the formation of an antigen depot in the skin lasting for several days and an increase in recruited immune infiltrates. Increased association of Poly(dG)-OVA is observed with MHC II- and CD11c-expressing cells in the skin compared to OVA. This is accompanied by the expression of pro-inflammatory CCL2 and IL-6 in the skin. Poly(dG)-OVA was also able to internalize more in skin migrating DCs and was transported more efficiently to draining lymph nodes. Poly(dG)-OVA immunization of B16-OVA-bearing mice contributed to delayed tumor progression and improved survival. We also developed Poly(dG)-Mgp10025–33 and Poly(dG)-TRP2180–188 to study melanoma-specific responses. Immunization with the these conjugates led to significant peptide-specific in vivo cytotoxic T cell responses compared to unconjugated peptides. Mice with B16 tumors immunized with combined Poly(dG)-Mgp100 Poly(dG)-TRP2 had delayed tumor progression and improved survival. Our results show that Poly(dG) conjugation of antigens is an effective strategy for the development of antitumor vaccines with improved immune responses.

Immunotherapy in Cancer: A Combat between Tumors and the Immune System; You Win Some, You Lose Some.

Cancer immunotherapy has emerged as a treatment modality, mainly as the result of discoveries in the immune response regulation, including mechanisms that turn off immune responses. Immunogenic cutaneous melanoma is a canonical model for therapeutic immunotherapy studies. “Passive” immunotherapy with monoclonal antibodies (mAbs) has outpaced “active” immunotherapy with anti-tumor vaccines, and mAbs that antagonize the off responses have been recently introduced in clinical practice. Despite these recent successes, many unresolved practical and theoretical questions remain. Notably unknown are the identity of the lymphocytes that eliminate tumor cells, which white cells enter into tumors, through which endothelium, in what order, and how they perform their task. The parameters of size and location that could be used to determine in which tumors the immune response may be sufficient to eradicate the tumor are yet unknown. Immunotherapy has been so far more efficient to treat solid and hematologic tumors located outside the central nervous system, than primary brain tumors and brain metastases. In contrast to recent advances with mAbs, anti-tumor vaccine development has been lagging behind. The multiplicity of antigens that must be targeted to achieve significant clinical response is partially responsible for this lag, especially in melanoma, one of the most mutated tumors. Further hampering vaccination results is the fact that tumor elimination by the immune system is the result of a race between tumors with different growth rates and the relatively slow development of the adaptive immune response. The enhancement of the native arm of the immune response or the administration of targeted chemotherapy to slow tumor development, are approaches that should be studied. Finally, criteria used to analyze patient response to immunotherapeutic treatments must be perfected, and the patient populations that could benefit the most from this approach must be better defined.

Exosomes from Dendritic Cells Loaded with Chaperone-Rich Cell Lysates Elicit a Potent T Cell Immune Response Against Intracranial Glioma in Mice.

Chaperone-rich cell lysates (CRCLs) may play an important role in the development of anti-tumor vaccines. Tumor-derived CRCLs have been reported to activate dendritic cells (DCs) to elicit potent anti-tumor activity. However, the role of DC-derived exosomes (DEXs) secreted from DCs loaded with CRCLs in the treatment of tumors has not been clearly determined. In the present study, DEXs were generated from DCs loaded with CRCLs derived from GL261 glioma cells. These DEXs, designated DEX (CRCL-GL261), were then used to treat DCs to create DEX (CRCL-GL261)-DCs. The DEX (CRCL-GL261)-DCs were found to promote cell proliferation and cytotoxic T lymphocyte (CTL) activity of CD4(+) and CD8(+) T cells in vitro compared with DEX (GL261)-DCs, which were loaded with DEXs derived from DCs loaded with GL261 tumor cell lysates. DEX (CRCL-GL261)-DCs significantly prolonged the survival of mice with tumors and inhibited tumor growth in vivo. In addition, DEX (CRCL-GL261)-DCs induced enhanced T cell infiltration in intracranial glioma tissues compared with other treatments. DEX (CRCL-GL261)-DCs induced strong production of anti-tumor cytokines, including interleukin-2 and interferon-γ. Moreover, depletion of CD4(+) and CD8(+) T cells significantly impaired the anti-tumor effect of DEX (CRCL-GL261)-DCs. Finally, DEX (CRCL-GL261)-DCs were found to negatively regulate Casitas B cell lineage lymphoma (Cbl)-b and c-Cbl signaling, leading to the activation of phosphatidyl inositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling in T cells. In summary, we present evidence that DEX (CRCL-GL261)-DCs induce more potent and effective anti-tumor T cell immune responses and delineate the underlying mechanism by which DEX (CRCL-GL261)-DCs exerted their anti-tumor activity through modulating Cbl-b and c-Cbl signaling. These results provide novel and promising insight for the development of an anti-tumor vaccine.

EXOSOMES DERIVED FROM THE ASCITIC FLUID OF MICE BEARING A T-CELL LYMPHOMA EXPRESS TUMOR ASSOCIATED ANTIGENS

EXOSOMES DERIVED FROM THE ASCITIC FLUID OF MICE BEARING A T-CELL LYMPHOMA EXPRESS TUMOR ASSOCIATED ANTIGENS

Using Mutant IDH1 to Arm the Immune System in Cancer

A new antitumor vaccine targets mutant IDH1.

Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell‐based cancer immunotherapy

Dendritic cell (DC)-based immunotherapy has recently demonstrated a great potential for clinical applications; however, additional progress in the methods of tumor-specific antigen delivery to DCs is necessary for the further development of anti-tumor vaccines. To this end, a capsid-optimized adeno-associated virus serotype 6 (AAV6-T492V+S663V) vector was developed by site-directed mutagenesis of surface-exposed serine (S) and threonine (T) residues, which have a critical role in intracellular trafficking of AAV vectors. This double-mutant AAV6 vector had ∼ 5-fold greater transduction efficiency in monocyte-derived DCs (moDCs) compared with wild-type (WT)-AAV6 vectors. The increase in the transduction efficiency correlated with the improved nuclear translocation of AAV6-T492V+S663V over that of the WT-AAV6 vector. Additional studies of the CD11c promoter identified critical regulatory elements that fit into the AAV expression cassette and drive EGFP expression in moDCs. Development of a chimeric promoter (chmCD11c) that contains functional modules of CD11c and a Simian virus (SV40) enhancer element dramatically increased the EGFP expression in moDCs. MoDCs transduced by the capsid-optimized AAV6 vector carrying human prostate-specific antigen (hPSA) driven by CBA (AAV6-T492V+S663V-CBA-hPSA) or chmCd11c (AAV6-T492V+S663V-chmCD11c-hPSA) generated specific T-cell clone proliferation and superior cytotoxic T lymphocytes (CTLs) with higher killing capability against human prostate adenocarcinoma cells, LNCaP, compared with WT-AAV6 induced CTLs. Taken together, these studies suggest that optimization of capsid and promoter components of AAV vectors can be a useful approach for efficient targeting of moDCs and may prove to be a promising tool for cancer immunotherapy.

Abstract B14: Minimum effective concentration of paclitaxel improves the effectivity of dendritic cells transfected with tumor RNA.

Abstract The central role of dendritic cells (DCs) in antigen presentation and induction of antitumor immunity supported the development of antitumor vaccines based on these cells. In previous studies, we have observed that treatment with ultra-low doses of paclitaxel (PAC) modulated human DCs to express the phenotype of mature and activated cells, and stimulated their antigen presentation activity. At the same time, tumor cells treated with low concentrations of drugs became more immunogenic and more susceptible to the lytic activity of cytotoxic T lymphocytes in vitro. Therefore, we aimed to verify if the transfection of DCs with drug-treated tumor cells RNA enhances the effectiveness of DC-based vaccines and if the in vitro effects are reproducible in vivo. Murine colon tumor cells (MC-38) were subcutaneously inoculated in C57Bl/6 mice. At the 10th and 17th days after inoculation, they received a DC vaccine transfected with RNA of MC-38 cells pre-treated with minimum effective concentration of PAC. These DCs expressed 12% higher levels of CD40 and were able to delay the tumor growth when compared with non-treated animals. Although the differences were not significant, our results suggest that the treatment of tumor cells with low concentration of PAC can enhance the immunogenicity of tumor cells, which is transfered for DCs by RNA transfection, and delay tumor growth. Financial support: FAPESP 2009/18331-8; FAPESP 2010/06013-9. Citation Format: Marcela Rodrigues Camargo, Cecília Pessoa Rodrigues, Carolina Mendonça Gorgulho, Fabiana Albani Zambuzi, Victória Elizabeth Galvão, Juliana Cristina Longo Frederico, Marcimara Penitenti, Ramon Kaneno. Minimum effective concentration of paclitaxel improves the effectivity of dendritic cells transfected with tumor RNA. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B14.

Fully Synthetic Self‐Adjuvanting Thioether‐Conjugated GlycopeptideLipopeptide Antitumor Vaccines for the Induction of Complement‐Dependent Cytotoxicity against Tumor Cells

Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-component vaccines that contained the Tetanus Toxoid P2 T-cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement-dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.

Tobacco Mosaic Virus as a New Carrier for Tumor Associated Carbohydrate Antigens

Tumor-associated carbohydrate antigens (TACAs) are being actively studied as targets for antitumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results of using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme-linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities toward Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.

Optimal MHC-II-restricted tumor antigen presentation to CD4+ T helper cells: the key issue for development of anti-tumor vaccines

Present immunoprevention and immunotherapeutic approaches against cancer suffer from the limitation of being not “sterilizing” procedures, as very poor protection against the tumor is obtained. Thus newly conceived anti-tumor vaccination strategies are urgently needed. In this review we will focus on ways to provide optimal MHC class II-restricted tumor antigen presentation to CD4+ T helper cells as a crucial parameter to get optimal and protective adaptive immune response against tumor. Through the description of successful preventive or therapeutic experimental approaches to vaccinate the host against the tumor we will show that optimal activation of MHC class II-restricted tumor specific CD4+ T helper cells can be achieved in various ways. Interestingly, the success in tumor eradication and/or growth arrest generated by classical therapies such as radiotherapy and chemotherapy in some instances can be re-interpreted on the basis of an adaptive immune response induced by providing suitable access of tumor-associated antigens to MHC class II molecules. Therefore, focussing on strategies to generate better and suitable MHC class II–restricted activation of tumor specific CD4+ T helper cells may have an important impact on fighting and defeating cancer.

Trypsin digest of cancer cells surface stimulates anti-tumor immune response better than cancer cells themselves

AbstractAntigens expressed on the surface of cancer cells are accessible targets for both humoral and cell-mediated immune responses, and are therefore potential candidates for vaccine development. Treating surface of live human breast adenocarcinoma cells (MCF-7) with trypsin yields a digest that contains 0.7% of total cell protein. Despite this difference, the trypsin digest stimulates in cytotoxicity assays anti-tumor response which kills 10-40% more cancer cells than those stimulated with cells themselves. From these results, we concluded that trypsin digest obtained from live cancer cells contains the essential antigens to induce an immune-mediated anti-tumor effect, and therefore, is candidate for anti-tumor vaccine development.

Trypsin digest of cancer cells surface stimulates anti-tumor immune response better than cancer cells themselves

Antigens expressed on the surface of cancer cells are accessible targets for both humoral and cell-mediated immune responses, and are therefore potential candidates for vaccine development. Treating surface of live human breast adenocarcinoma cells (MCF-7) with trypsin yields a digest that contains 0.7% of total cell protein. Despite this difference, the trypsin digest stimulates in cytotoxicity assays anti-tumor response which kills 10-40% more cancer cells than those stimulated with cells themselves. From these results, we concluded that trypsin digest obtained from live cancer cells contains the essential antigens to induce an immune-mediated anti-tumor effect, and therefore, is candidate for anti-tumor vaccine development.

DNA vaccines for the treatment of prostate cancer

Prostate cancer is a significant public health problem, and the most commonly diagnosed cancer in the USA. The long natural history of prostate cancer, the presence of a serum biomarker that can be used to detect very early recurrences, and the previous identification of multiple potential tissue-specific target antigens are all features that make this disease suitable for the development of anti-tumor vaccines. To date, many anti-tumor vaccines have entered clinical testing for patients with prostate cancer, and some have demonstrated clinical benefit. DNA vaccines represent one vaccine approach that has been evaluated in multiple preclinical models and clinical trials. The safety, specificity for the target antigen, ease of manufacturing and ease of incorporating other immune-modulating approaches make DNA vaccines particularly relevant for future development. This article focuses on DNA vaccines specifically in the context of prostate cancer treatment, focusing on antigens targeted in preclinical models, recent clinical trials and efforts to improve the potency of these vaccines.