Cancer Immunotherapy

Ovarian Cancer

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Ovarian cancer is one of the major cancer types for which powerful, immune-based cancer treatments are now in development. This page features information on ovarian cancer and immunotherapy clinical trials for ovarian cancer patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to ovarian cancer patients.

Ovarian cancer is the leading cause of death from gynecologic cancer in the United States. Each year nearly 21,290 women in the United States will be diagnosed with ovarian cancer, and 14,180 will die. Ovarian cancer is sometimes called “the cancer that whispers,” because the disease often progresses before symptoms arise. Nine out of 10 ovarian cancers are epithelial ovarian cancers— deriving from the outer (epithelial) layer of the ovary.

The most important risk factor for ovarian cancer is a strong family history of breast or ovarian cancer. Women who have had breast cancer or who have tested positive for inherited mutations in BRCA1 or BRCA2 genes are at increased risk.

Despite advances in surgery and chemotherapy over the past 20 years, only modest progress has been made in improving overall survival in patients with ovarian cancer. Although the majority of women with advanced ovarian cancer respond to first-line chemotherapy, most responses are not durable. More than 80% of patients will have a recurrence of their disease after first-line treatment, and more than half will die of recurrent disease within 5 years of diagnosis.

The poor survival in advanced ovarian cancer is due both to late diagnosis, as well as to the lack of effective second-line therapy for patients who relapse. The clinical course of ovarian cancer patients is marked by periods of remission and relapse of sequentially shortening duration until chemotherapy resistance develops. Therefore, new treatment modalities and paradigms are needed in order to significantly improve the prognosis of women diagnosed with epithelial ovarian cancer.


First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment, which achieves a complete response in approximately 80% of patients. (A complete response means no visible evidence of disease on imaging scans and normal blood tests.) Patients who respond but who relapse after a period of six months or more may undergo the same therapy. Patients who progress during first-line treatment or who relapse within six months following successful first-line treatment are considered refractory or resistant to platinum-based treatments. For these patients, there are several chemotherapeutic options; however, each has shown only marginal benefit. Therefore, patients with platinum-resistant disease are encouraged to enter clinical trials.

When Should Ovarian Cancer Patients Consider A Clinical Trial?

Women with stage 1, grade 1 tumors (in whom survival is greater than 95% after comprehensive surgery), do not generally need to consider clinical trials. Patients in all other stages of ovarian cancer are encouraged to enter clinical trials for both primary and recurrence therapy. Specifically, clinical trials may be recommended for the following:

  • Patients with stage 2, 3, and 4 ovarian cancer who are in complete remission after first-line treatment;
  • If cancer doesn’t respond to or progresses during first-line treatment;
  • Cancer recurs within 6 months of first-line treatment after complete remission;
  • Cancer that is stage 2, 3, or 4 and only partly responds to chemotherapy (“partly shrunk”);
  • Cancer recurs more than 6 months after complete remission with first-line chemotherapy;
  • Cancer responds to second or subsequent lines of chemotherapy, and the patient is in remission;
  • Cancer responds to second or subsequent lines of chemotherapy, but recurs again.
A number of immune-based therapies are being investigated in early-phase clinical trials for patients with ovarian cancer. Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.


Current immunotherapies for ovarian cancer fall into five broad categories: monoclonal antibodies; checkpoint inhibitors and immune modulators; therapeutic vaccines; adoptive T cell transfer; and oncolytic viruses. These therapies are still in early-phase testing (phase I and II) for ovarian cancer, but their successful use in other types of cancers suggests that they may ultimately prove useful for ovarian cancer as well.

Monoclonal Antibodies

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Bevacizumab (Avastin®), which targets vascular endothelial growth factor (VEGF), is FDA-approved for the treatment of ovarian cancer. Several monoclonal antibodies are currently being tested in clinical trials:

  • A phase II trial of DNIB0600A, an antibody conjugated to the anti-mitotic agent MMAE, for patients with platinum-resistant ovarian cancer (NCT01991210).
  • A phase Ib/II trial to test demcizumab (OMP-21M18), a monoclonal antibody targeting Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway (which is known to be important in cancer stem cells and cancer), in patients with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer (NCT01952249).
  • A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with epithelial cancers (NCT01631552).
  • A phase I trial to test OMP-52M51, an anti-Notch1 antibody, in patients with solid tumors (NCT01778439).

Checkpoint Inhibitors and Immune Modulators

Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.

  • Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
  • MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
    • A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
    • A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
    • A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
    • MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
  • A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
  • Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
  • A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
  • A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
  • A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
  • A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
  • A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).

Therapeutic Vaccines

Scientists have identified several ovarian cancer-associated antigens—molecules on or in cells that are capable of eliciting an immune response—that can serve as targets for immune recognition and attack. These include several “cancer-testis” antigens, which are expressed only by cancer cells and not by healthy tissues (with the exception of the testis and, occasionally, placenta), making them promising targets for cancer immunotherapy. One of these, NY-ESO-1, is under intense investigation by researchers in the CRI/Ludwig Clinical Trials Network. Research by CRI investigator Kunle Odunsi, M.D., Ph.D., has shown that NY-ESO-1 expression may be found in up to 43% of ovarian cancers.

Several phase I and II studies of antigen-based vaccines are currently recruiting patients with ovarian cancer, including:

  • A phase II trial of a dendritic cell vaccine for patients with advanced ovarian cancer (NCT00703105).
  • A phase II trial of FANG vaccine, being developed by Gradalis, plus bevacizumab for patients with recurrent/refractory ovarian cancer (NCT01551745).
  • A phase II trial of TroVax® (MVA-5T4), targeting the 5T4 antigen and being developed by Oxford BioMedica, versus placebo in patients with relapsed asymptomatic ovarian cancer (NCT01556841).
  • A phase I/II trial combining INCB024360, an IDO1 inhibitor, CDX-1401, which targets the NY-ESO-1 protein, and Poly-ICLC, a Toll-like receptor 3 stimulant, in ovarian, fallopian tube, or primary peritoneal cancer in remission (NCT02166905).
  • A phase I/II trial of DCVax, being developed by Northwest Biotherapeutics, in patients with solid tumors (NCT01882946).
  • A phase I trial of two peptide vaccines, E39 and J65, in patients with breast or ovarian cancer who have been treated and are without evidence of disease (NCT02019524).
  • A phase I trial in metastatic solid tumors, including ovarian cancer, of a vaccine targeting the HER2 antigen (NCT01376505).
  • A phase I trial testing ID-LV305, a vaccine targeting the NY-ESO-1 antigen and being developed by Immune Design, in patients with solid tumors, including ovarian cancer (NCT02122861).
  • A phase I trial of dendritic cell vaccine therapy given with or without sirolimus in patients with solid tumors expressing NY-ESO-1 (NCT01522820).

Adoptive T Cell Transfer

A fourth major avenue of immunotherapy for ovarian cancer is adoptive T cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several phase I and II trials of adoptive T cell transfer techniques are currently under way for patients with ovarian cancer, including:

  • White blood cells genetically engineered to recognize NY-ESO-1, given along with dendritic cells pulsed with NY-ESO-1 antigen as a vaccine, in a phase II trial for patients with stage IV, advanced, or refractory malignancies (NCT01697527).
  • A phase I/II trial to test T cells genetically engineered to target VEGFR (a protein necessary for blood vessel formation) in patients with metastatic cancer, including ovarian cancer (NCT01218867).
  • A phase I/II trial to test T cells genetically engineered to target the MAGE-A3 or NY-ESO-1 antigens in patients with ovarian cancer (NCT01567891).
  • A phase I trial to test chimeric antigen receptor (CAR) T cell therapy targeting mesothelin, which is overexpressed in ovarian cancer, pancreatic cancer, and mesothelioma, at the University of Pennsylvania (NCT02159716).

Oncolytic Viruses

Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase I/II trial to test the oncolytic measles virus in patients with ovarian cancer that has recurred (NCT02068794).
  • A phase I trial to test AdV-tk, an oncolytic herpes simplex virus being developed by Advantagene, in patients with solid tumors, including ovarian cancer (NCT01997190).

Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.

CRI Contributions and Impact

Immunotherapy as a potentially promising treatment for ovarian cancer is based on several lines of evidence. The earliest and one of the most striking came from observations that the presence of infiltrating T cells (called “tumor-infiltrating lymphocytes,” or TILs) in ovarian tumors is positively and strongly associated with improved survival of patients with ovarian cancer [1]. A later study by CRI scientists confirmed that patients with higher frequencies of infiltrating killer T cells had improved survival [2]. Together, these and other findings strongly suggest that immunotherapies that can induce or enhance optimal immunologic conditions within ovarian cancers may hold great promise for extending the lives of ovarian cancer patients.

Since 1985, CRI has made more than 75 grants totaling more than $16 million in new research and treatment approaches for ovarian cancer. Recent results and studies include:

  • In a study by CRI investigator Kunle Odunsi, M.D., Ph.D., at Roswell Park Cancer Institute, patients in first remission treated with a NY-ESO-1 cancer vaccine showed a median time to progression of 21 months compared with a historical average of 16 months [3]. A more recent CRI-funded trial in ovarian cancer patients suggests even more promising results. CRI scientists treated 28 patients with ovarian cancer in second or third remission using a cancer vaccine composed of overlapping peptides of NY-ESO-1 administered with the immune stimulants Montanide® and Poly-ICLC (Hiltonol®). The combination was successful in achieving the most powerful anti-cancer immune responses seen to date in a CRI study. Moreover, patients whose cancers expressed the NY-ESO-1 vaccine target had an average time to progression of 22 months, compared to an average of 4 months among patients whose cancers lacked NY-ESO-1 expression [4]. The time to relapse of 22 months is particularly notable because this interval for patients in second or third remission is typically shorter than for patients in first remission, with averages from 4 to 10 months or less. The results of the study provide an important foundation for further clinical development of this immunotherapeutic strategy, particularly in combination with checkpoint blockade therapies.
  • In a 2013 paper published in the journal Cancer Immunology Research, Kunle Odunsi and colleagues showed that a drug called decitabine can increase the effectiveness of a vaccine targeting the NY-ESO-1 antigen. Six of ten patients with refractory epithelial ovarian cancer who received this treatment showed either stable disease or had a partial regression of their tumors [5].
  • Dr. Odunsi and members of CRI’s Ovarian Cancer Working Group have also shown that the enzyme indoleamine-2,3-dioxygenase (IDO) is critical in mediating immunosuppression in the ovarian tumor microenvironment, and that blocking IDO can successfully prevent tumor-mediated suppression of T cells. Two new clinical trials that block IDO activity are open to patients with ovarian cancer (NCT02042430, NCT02166905).
  • CRI-funded studies have also shown that targeting multiple immunosuppressive pathways in ovarian cancer may be another promising approach. Dr. Odunsi and his collaborators have shown that two inhibitory molecules, PD-1 and LAG-3, collaborate in suppressing the anti-tumor T cell immune response [6]. Moreover, by giving a combination of antibodies that block PD-1 and LAG-3, they could restore T cells to full function resulting in stronger anti-tumor immunity. A phase I LAG-3 clinical trial, with or without PD-1 therapy, is under way in patients with solid tumors (NCT01968109).
  • Members of the Ovarian Cancer Working Group, Danila Valmori, Ph.D., and Maha Ayyoub, Ph.D., at the Centre de Lutte Contre le Cancer-Nantes Atlantique in France, have made important discoveries about the roles and characteristics of different immune cells in ovarian cancer, including the Th17 subset of helper T cells and regulatory T cells. Their studies are giving us important clues about how we can effectively target different immune cell subsets to improve ovarian cancer immunotherapy.
  • David Lampi Hermanson, Ph.D., a 2014-2017 CRI postdoctoral fellow at the University of Minnesota, is investigating the use of natural killer (NK) cell-based immunotherapy for ovarian cancer. NK cells are a key part of the innate immune system with the ability to recognize and kill diverse types of tumor cells, including ovarian cancer. In the proposed project, Dr. Lampi Hermanson will produce NK cells from stem cells, inserting a chimeric antigen receptor (CAR) with the capacity to recognize mesothelin cells, which is expressed in 70% of ovarian cancer patients. This approach has the potential to provide a novel immunotherapy for women with ovarian cancer.
  • Juan R. Cubillos-Ruiz, Ph.D., a 2012-2014 CRI postdoctoral fellow at Weill Cornell Medical College, is working to understand how dendritic cells (DCs), immune cells responsible for activating and “training” other immune cells, acquire pro-tumor properties in ovarian cancer. His goal is to develop strategies to re-educate DCs to promote anti-cancer immune responses. He has found a protein, XBP1, that may represent a highly promising target for immunotherapies aimed at boosting pre-existing anti-ovarian cancer immune responses. He is also exploring how therapies that target XBP1 might synergize with other immunotherapies such as adoptive T cell transfer and CD40 antibodies.

Sources: National Cancer Institute Physician Data Query (PDQ); American Cancer Society Facts & Figures 2015; GLOBOCAN 2012; National Comprehensive Cancer Network (NCCN) Guidelines for Patients;; CRI grantee progress reports and other grantee documents

Last Updated March 2015

[1] Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003 Jan 16;348(3):203-13. PMID: 12529460 (

[2] Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 2005 Dec 20;102(51):18538-43. PMID: 16344461 (

[3] Odunsi K, Matsuzaki J, Karbach J, Neumann A, Mhawech-Fauceglia P, Miller A, Beck A, Morrison CD, Ritter G, Godoy H, Lele S, duPont N, Edwards R, Shrikant P, Old LJ, Gnjatic S, Jäger E. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. Proc Natl Acad Sci U S A 2012 Apr 10;109(15):5797-802. PMID: 22454499 (

[4] Sabbatini P, Tsuji T, Ferran L, Ritter E, Sedrak C, Tuballes K, Jungbluth AA, Ritter G, Aghajanian C, Bell-McGuinn K, Hensley ML, Konner J, Tew W, Spriggs DR, Hoffman EW, Venhaus R, Pan L, Salazar AM, Diefenbach CM, Old LJ, Gnjatic S. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res 2012 Dec 1;18(23):6497-508. PMID: 23032745 (

[5] Odunsi K, Matsuzaki J, James SR, Mhawech-Fauceglia P, Tsuji T, Miller A, Zhang W, Akers SN, Griffiths EA, Miliotto A, Beck A, Batt CA, Ritter G, Lele A, Gnjatic S, and Karp AR. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol Res. 2013;2(1):1-13.

[6] Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, Eppolito C, Qian F, Lele S, Shrikant P, Old LJ, Odunsi K. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A 2010 Apr 27;107(17):7875-80. PMID: 20385810 (


Ovarian Cancer News & Stories

Reviewed By:

Kunle Odunsi is an expert in ovarian cancer immunotherapy
Kunle Odunsi, M.D., Ph.D.
Roswell Park Cancer Institute, Buffalo, NY

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