Immunotherapy for Ovavian Cancer

Immunotherapy for Ovavian Cancer: Review

Immunotherapy for ovavian cancer could be effective as ovavian cancer cells express immunogenic tumor-associated antigens that elicit detectable, specific immune responses. The positive correlation between ovavian cancer survival and tumor infiltration with CD8+ T cells is compelling evidence that anti-tumor immune surveillance is a critical dictate of clinical outcomes in ovavian cancer. Despite abundant evidence that anti-tumor immunity in ovavian cancer could be effective, immune-based ovavian cancer therapies have generally been only modestly successful, at best.

Immunotherapy for ovavian cancer: monoclonal antibodies

Anti-milk fat globulin-1: The first therapeutic antibodies to treat human ovavian cancer were anti-human milk fat globulin-1 antibodies radiolabeled and injected into the peritoneum.
Farletuzumab: Farletuzumab is a humanized anti-folate receptor-α antibody thought to function not through blocking folate transport but through antibody dependent cellular cytotoxicity.
Catumaxomab: Catumaxomab is a trifunctional antibody that kills EpCAM-expressing tumor cells, the primary cause of malignant ascites.
Anti-CTLA4: Ipilimumab and tremelimumab are fully human IgG1 or IgG2 antibodies, respectively, that antagonize the CTLA-4 immune checkpoint. Ipilimumab is FDA-approved to treat metastatic or unresectable melanoma and is the first standard-of-care immune checkpoint inhibitor. Anecdotal reports of ovavian cancer responses to ipilimumab and pre-clinical findings prompted an ongoing phase II trial of ipilimumab for platinum-resistant ovavian cancer (NCT01611558). Ipilimumab can cause significant autoimmune side effects. Tremelimumab (in phase III trials for melanoma) could have similar efficacy with reduced toxicities.
Anti-PD-L1: BMS-936559 is a fully human IgG4 monoclonal antibody that blocks PD-L1 from binding its two known receptors PD-1 and CD80.
Oregovomab: CA-125 was targeted in vivo by the murine IgG1 monoclonal antibody oregovomab.
Abagovomab: Abagovomab is an anti-idiotypic CA-125 murine monoclonal antibody[41] that induces anti-CA-125 antibodies.
Volociximab: Volociximab is a chimeric IgG4 monoclonal antibody against AAB1, a component of α5β1 integrin that is anti-angiogenic.
Amatuximab: Mesothelin is a tumor differentiation antigen over-expressed in certain cancers including those of ovary, pancreas and mesothelium. Amatuximab is a chimeric anti-mesothelin monoclonal antibody.
Siltuximab: IL-6 in an important immunopathologic cytokine in distinct tumors and plays diverse immunopathogenic roles in ovavian cancer. Siltuximab is an anti-IL-6 antibody being tested as treatment for various carcinomas, hematologic malignancies and tumor cachexia.
Tocilizumab: Tocilizumab is a humanized anti-IL-6 receptor antibody being tested for cancer cachexia and is used to mitigate cytokine release symptoms in adoptive T cell therapy.
Anti-CD137: CD137 (4-1BB) is a stimulatory T cell co-receptor that enhances T cell proliferation and cytolytic activity.

Immunotherapy for ovavian cancer: cytokines

Interferon-α: Interferon-α is the principal type I interferon tested for human anti-cancer activity. Intraperitoneal interferon-α to treat OC was first assessed in the early 1980's.
Interferon-γ: Interferon-γ was used to treat ovavian cancer by 1992, and by 1996, intraperitoneal interferon-γ elicited some encouraging preliminary results.
Interleukin (IL)-2: IL-2, a T cell growth and activator factor, exerts modest anti-cancer activity in melanoma and renal cell carcinoma, among other cancers. IL-2 at low doses was combined with retinoic acid in an ovavian cancer trial.
Tumor necrosis factor (TNF)-α: Tumor necrosis factor (TNF)-α.
IL-18: Recombinant IL-18 is an immunostimulatory cytokine that boots antitumor immunity in combination with pegylated liposomal doxorubicin in mouse models.

Immunotherapy for ovavian cancer: vaccines

Many ovavian cancer patients have easily detectable numbers of functional tumor antigen specific T cells, suggesting that augmenting tumor-specific immunity could lead to improved clinical benefits. A number of tumor-associated antigens have been detected in ovavian cancer, any of which potentially could help elicit beneficial anti-tumor- immunity. These tumor-associated antigens include HER2/neu, MUC1, NY-ESO-1, membrane folate receptor, folate binding protein (gp38), TAG-72, mesothelin, sialyl-Tn, milk fat globulin-1, OA3, P53, Carcinoembryonic antigen glypican-3 (GPC3) and Carcinoembryonic antigen (CEA).

Immunotherapy for ovavian cancer: adoptive cell transfers

The adoptive cell transfers in ovavian cancer include Dendritic cells (DC), T cells, and Oncolytic viruses.
Over the next several years we expect that important advances in ovavian cancer immunotherapy will be made, leading to important phase II and III trials.

Immunotherapy for Ovavian Cancer: Reference

Drerup J M et al. Immunotherapy for Ovarian Cancer[J]. Current treatment options in oncology, 2015, 16(1): 1-20.
Riva P, et al. Locoregional immunotherapy of human ovarian cancer: preliminary results. Int J Rad Appl Instrum B. 1989;16(6):659–66.