Antigen-specific vaccines for cancer treatment

Abstract

Vaccines targeting pathogens are generally effective and protective because based on foreign non-self antigens which are extremely potent in eliciting an immune response. On the contrary, efficacy of therapeutic cancer vaccines is still disappointing. One of the major reasons for such poor outcome, among others, is the difficulty of identifying tumor-specific target antigens which should be unique to the tumors or, at least, overexpressed on the tumors as compared to normal cells. Indeed, this is the only option to overcome the peripheral immune tolerance and elicit a non toxic immune response. New and more potent strategies are now available to identify specific tumor-associated antigens for development of cancer vaccine approaches aiming at eliciting targeted anti-tumor cellular responses. In the last years this aspect has been addressed and many therapeutic vaccination strategies based on either whole tumor cells or specific antigens have been and are being currently evaluated in clinical trials. This review summarizes the current state of cancer vaccines, mainly focusing on antigen-specific approaches.

Keywords: APCs, antigen-presenting cell; BCG, Bacille Calmette-Guerin; BCR, B-cell receptor; CDCA1, cell division cycle associated 1; CRC, colorectal cancer; CT, Cancer-testis; CTL, cytotoxic T-lympocites; DCs, dendritic cells; EGT, electro-gene-transfer; FDA, Food & drug administration; GB, glioblastoma; GM-CSF, granulocyte macrophage-colony stimulating factor; HER2, human epidermal growth factor receptor 2; HLA, human leukocyte antigen; HPV, human papillomavirus; HSPs, stress/heat shock proteins; IFNg, interferon gamma; Ig Id, immunoglobulin idiotype; LPs, long peptides; MAGE-A1, Melanoma-associated antigen 1; MHC, major histocompatibility complex; MS, mass spectrometry; MVA, modified vaccinia strain Ankara; NSCLC, non-small-cell lung carcinoma; PAP, prostatic acid phosphatase; PRRs, Pattern Recognition Receptors; PSA, Prostate-specific antigen; RCR, renal cell cancer; SSX-2, Synovial sarcoma X breakpoint 2; TAAs, tumor-associated antigens; TACAs, Tumor-associated carbohydrate antigens; TARP, T-cell receptor gamma alternate reading frame protein; TLRs, Toll-Like Receptors; TPA, transporter associated with antigen processing; WES, whole exome sequencing; WGS, whole genome sequencing; cancer vaccine; clinical trials; epitopes; hTERT, human Telomerase reverse transcriptase; immunotherapeutics; mCRPC, metastatic castrate-resistant prostate cancer; tumor-associated antigens.

Figure 1.

Cumulative numbers of cancer vaccine clinical trials for each cancer and each vaccination strategy.

Figure 2.

Number of cancer vaccine clinical trials in each experimental phase for each vaccination strategy.