Whole Tumor Antigen Vaccines: Where Are We?

Chiang, Cheryl Lai-Lai; Coukos, George; Kandalaft, Lana E.

doi:10.3390/vaccines3020344

Cited by 217 publications

(192 citation statements)

References 123 publications

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“…Vaccination of patients with their own cancer cells (autologous cell vaccine) has been tried in the past with variable success (32,33). Most have used mixing the whole cell vaccine with nonspecific adjuvants, such as BCG, but difficulties in overcoming immune suppression within the tumor microenvironment have limited results (34).…”

Section: Discussionmentioning

confidence: 99%

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

Alkayyal

Tai

Kennedy

et al. 2017

Cancer Immunology Research

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Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.

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Section: Discussionmentioning

confidence: 99%

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

Alkayyal

Tai

Kennedy

et al. 2017

Cancer Immunology Research

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“…31 Unlike vaccines that use specific CAAs, whole tumor antigen vaccines are available for all types of cancers. Furthermore, they target multiple epitopes that can induce an immune response.…”

Section: Discussionmentioning

confidence: 99%

Whole cell vaccination using immunogenic cell death by an oncolytic adenovirus is effective against a colorectal cancer model

Yamano

Kubo

Fukumoto

et al. 2016

Molecular Therapy - Oncolytics

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Cancer vaccine application is limited to specific cancer types because few cancer-associated antigens are known to induce tumor rejection. Accordingly, we assessed the utility of Ad881, an oncolytic adenovirus in which viral replication was strictly regulated by the cancer-specific midkine promoter, as a cancer vaccine in a murine colorectal cancer model lacking specific cancer-associated antigens. In CT26 and CMT93 cells, Ad881 (multiplicity of infection: 100 or 1,000) showed stronger cytotoxicity and oncolysis in vitro than its equivalent replication-defective adenovirus, Ad884. CT26 cells (1 × 104) infected with Ad881 (multiplicity of infection: 1,000) for 24 hours were suitable as vaccine antigens without tumor formation in our model. Repeated vaccinations, but not single vaccination, induced a greater prophylactic immune response. The percentage of mice that rejected the tumor challenge was 0, 4, and 38% after no vaccination, single vaccination, and repeated vaccinations, respectively. Immunogenic cell death marker high-mobility group box 1 protein (HMGB1) and adenosine triphosphate in culture medium were higher after Ad881 infection (24.3 ng/ml and 48.2 nmol/l, respectively) than after Ad884 infection (8.6 ng/ml and 15.4 nmol/l, respectively) or oxaliplatin treatment (3.7 ng/ml and 1.8 nmol/l, respectively). These results indicate that repeated whole cell vaccination using an oncolytic adenovirus may be a potent approach to evoke immunogenic cell death.

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“…Furthermore, with increasing knowledge on the immune system's function, it has become increasingly clear that vaccines that are produced on the basis of tumor cell lysate may not always confer a therapeutic benefit. One major obstacle of lysate-based vaccines is the presence of tumor antigens derived from self proteins, which may be subject to peripheral and central immunological tolerance mechanisms and thereby preclude powerful immune responses [47]. Accordingly, despite more than 2 decades of research on tumor lysate-based vaccines, only limited progress has been made [48].…”

Section: Vaccinationmentioning

confidence: 99%

Immunotherapy of Brain Cancer

2016

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The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors.

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Whole Tumor Antigen Vaccines: Where Are We?

Cited by 217 publications

References 123 publications

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

Whole cell vaccination using immunogenic cell death by an oncolytic adenovirus is effective against a colorectal cancer model

Immunotherapy of Brain Cancer

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