Hum Vaccin Immunother. 2014;10(11):3332-46. doi: 10.4161/21645515.2014.973317.
Antigen-specific vaccines for cancer treatment.
1a Laboratory of Molecular Biology and Viral Oncology; Department of Experimental Oncology; Istituto Nazionale per lo Studio e la Cura dei Tumori; “Fondazione Pascale” – IRCCS ; Naples , Italy.
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 ofcancer 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.
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 lungcarcinoma; 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
PLoS One. 2014 Apr 3;9(4):e93886. doi: 10.1371/journal.pone.0093886. eCollection 2014.
Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients.
1Biotherapy Center, Qingdao Center Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao, China.
2Department of Radiation Oncology, NCI-Designated Comprehensive Cancer Center, University of California at Davis Sacramento, Sacramento, California, United States of America.
3Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells. Cytokine levels in patients’ sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.
Cancer Immunol Immunother. 2011 Oct;60(10):1383-95. doi: 10.1007/s00262-011-1036-0. Epub 2011 Jun 3.
Low molecular weight hyaluronan preconditioning of tumor-pulsed dendritic cells increases their migratory ability and induces immunity against murine colorectal carcinoma.
- 1Gene Therapy Laboratory, School of Medicine, Austral University, Avenida Presidente Perón 1500 (B1629ODT) Derqui-Pilar, Buenos Aires, Argentina. firstname.lastname@example.org
We have recently shown that systemic administration of low molecular weight hyaluronan (LMW HA) significantly reduces colorectal carcinoma(CRC) growth in vivo. The elicited response is partially mediated by activated dendritic cells (DC). To potentiate the ability of DC loaded with whole tumor lysate (DC/TL) to induce immunity against CRC in mice, we aimed to study the effects of preconditioning DC with LMW HA for therapeuticvaccination. LMW HA improved maturation of ex vivo generated DC, increased IL-12, decreased IL-10 production, and enhanced a MLR activity in vitro. Although TNF-α showed a similar capacity to mature DC, preconditioning of DC/TL with LMW HA increased their ability to migrate in vitro toward CCL19 and CCL-21 in a CD44- and a TLR4-independent manner; this effect was superior to Poly(I:C), LPS, or TNF-α and partially associated with an increase in the expression of CCR7. Importantly, LMW HA dramatically enhanced the in vivo DC recruitment to tumor-regional lymph nodes. When these LMW HA-treated CRC tumor lysate-pulsed DC (DC/TL/LMW HA) were administered to tumor-bearing mice, a potent antitumor response was observed when compared to DC pulsed with tumor lysate alone and matured with TNF-α. Then, we showed that splenocytes isolated from animals treated with DC/TL/LMW HA presented a higher proliferative capacity, increased IFN-γ production, and secreted lower levels of the immunosuppressive IL-10. Besides, increased specific CTL response was observed in DC/TL/LMW HA-treated animals and induced long-term protection against tumor recurrence. Our data show that LMW HA is superior to other agents at inducing DC migration; therefore, LMW HA could be considered a new adjuvant candidate in the preparation of DC-based anticancer vaccines with potent immunostimulatory properties.
Keywords: Hyaluronan; Dendritic cells; Migration; CD44; TLR4; Colorectal carcinoma