Immunotherapy in ovarian cancer

Figures & data

Table 1. Immunotherapeutic strategies under investigation in Ovarian Cancer

Innate Immunity	Adaptive Immunity	Immunomodulation
Cytokines	Peptide vaccines	Treg blockade
Adoptive transfer of NK cells	Viral-based peptide vaccines	CTLA-4 blockade
	Whole tumor antigen vaccine	Pegylated liposomal doxorubicin
	Monoclonal antibodies
	Adoptive transfer of T cells
	Dendritic cell-based vaccines

Table 2. Peptide-based Vaccines studied in Ovarian Cancer

Target	MHC-I or MHC-II restricted	Phase	Reference	Clinical Response	Immune Response
HER2/neu	II	I/II	27,28	NA	HER2/neu-specific IgG antibody and T cell responses
NY-ESO-1	both	I	29	NA	NY-ESO-1 specific CD4 and CD8 T cell responses
	I	I	30	3 CR 6 PD	NY-ESO-1 specific CD8 T cell responses
p53	I	II	31	2 NED 12 RD	p53-specific CD8 T cell responses
	n/a	II	32,33	2 SD 18 PD	p53-specific, Th2 dominant CD4 T cell responses
WT-1	I	Case report	34	SD x 1 y	Weak correlation between CA125 and the mononuclear phagocyte/lymphocyte ratio
	I	II	35	1 SD 4 PD 1 NE	NA
STn	II	I	36	3 CR 2 PD 2 NA	Anti-STn Th1 T cell responses
	NA	II	37	Median OS 12.7 mo	Anti-STn IgG and IgM antibody responses, Anti-OSM (ovine submaxillary mucin) antibody responses
Lewis^y	NA	I	44	5 NED 19 RD	Anti- Lewis^y antibody responses

NA, not available; CR, complete response; PD, progressive disease; n/a, not applicable, NED, no evidence of disease; RD, recurrent disease; SD, stable disease; NE, not evaluable

Table 3. Monoclonal Antibodies studied in Ovarian Cancer

Antibody	Target	Reference	Phase	Clinical Response	Immune Response
Oregovomab	CA125	49	II	3 SD 10 PD	Oregovomab and CA125-specific antibody and T cell responses
		50	I	4 NED 2 CR 7 PD	HAMA, anti-oregovomab and anti-CA125 antibodies
Abagovomab	CA125	53	I	NA	HAMA, anti-anti-idiotypic and antiCA125 antibodies, CA125-specific CD4 and CD8 T cells
		54	Ib/II	4 CR 30 SD 62 PD 23 NA	Anti-anti-idiotypic and antiCA125 antibodies, Antibody dependent cell-mediated cytotoxicity
		55	I	12 SD 21 PD	HAMA and anti-anti-idiotypic antibodies, CA125-specific IFN-γ producing T cells
HMFG1	MUC1	56	I	1 SD 25 RD	Anti-HMFG1 and anti-MUC1 antibodies
Catumaxomab	EpCAM, CD3	60,61	II/III	Longer puncture-free survival and time to next paracentesis	Human anti-mouse antibodies
Trastuzamab	HER2/neu	63	II	1 CR 2 PR 16 SD 22 PD	No anti-trastuzumab antibody formation
MOv18	FR-α	65	I	NA	No anti-c-MOv18 antibodies
MORAb-003	FR-α	66	I	9 SD 16 PD 1 NE	Limited anti-MORAb-003 antibodies
Bevacizumab	VEGF	69	II	2 CR 11 PR 32 SD 17 PD	NA
		70	II	0 CR 7 PR 27 SD 5 PD 5 NE	NA
		67	III	168 Responders (CR/PR) 82 Non-responders (SD/PD) 7 unknown	NA
		68	III	No difference in OS; significant improval in PFS	NA

SD, stable disease; PD, progressive disease; NED, no evidence of disease; CR, complete response; HAMA, human anti-mouse antibody; NA, not available; RD, recurrent disease; NE, not evaluable

Table 4. Current Clinical Trials investigating Immunotherapy in Ovarian Cancer

Trial Identifier	Phase	Objective
Cytokines
NCT00003408	II	To study the effectiveness of biological therapy with sargramostim (GM-CSF), IL-2 and INF-α following high-dose chemotherapy and autologous stem cell transplantation in treating patient who have cancer (including ovarian cancer)
NCT00157573	II	To examine the ability of GM-CSF to alter disease progression in women who have recurrent but asymptomatic recurrence of their ovarian, fallopian tube or primary peritoneal cancer
NCT00659178	I	To assess the safety and biological activity of IL-18 (SB-485232) IV infusion in combination with Doxil in Advanced Stage Epithelial Ovarian Cancer
Vaccines
NCT00001827	II	To determine the safety and immunogenicity of vaccination with a p53 peptide in ovarian cancer patients
NCT00017537	I	To study the effectiveness of MVF-HER-2(628–647) and CRL1005 Copolymer Adjuvant in Patients with metastatic cancer (including ovarian cancer)
NCT00088413	I	To evaluate the safety and tolerability of PANVAC-V priming vaccine and PANVAC-F boosting vaccine, which produce CEA and MUC-1, in combination with sargramostim (GM-CSF) in adults with metastatic carcinoma including ovarian cancer
NCT00423254	I	To evaluate the safety and immune response to DNA Vector pPRA-PSM With Synthetic Peptides E-PRA and E-PSM, a multi-component immune based therapy, in patients with advanced cancer, including ovarian cancer
NCT00437502	I	To evaluate the safety of a peptide vaccine (consisting of 12 different tumor-rejection antigens) plus GM-CSF and Adjuvant (Montanide ISA-51) as Consolidation Following Optimal Debulking and Systemic Chemotherapy for Women with Advanced Stage Ovarian, Tubal or Peritoneal Cancer
NCT00585845	I	To evaluate the safety and tolerability of CRS207, a live attenuated Listeria monocytogenes expressing human mesothelin, in patients with advanced cancer of the ovary or pancreas, non-small cell lung cancer or advanced malignant epithelial mesothelioma
NCT00660101	I/II	To determine the safety and efficacy of a DNP-Modified Autologous Ovarian Tumor Cell vaccine as therapy in ovarian cancer patients after relapse
NCT00948961	I/II	To examine the safety and tolerability of CDX-1401 in combination with Resiquimod and/or Poly-ICLC in patient with advanced cancers that are known to express the NY-ESO-1 protein (including ovarian cancer)
NCT01095848	I	To determine the safety and immunogenicity profile of DPX-0907 (consisting of 7 tumor-specific HLA-A2-restricted peptides, a universal T helper peptide, a polyneucleotide adjuvant, a liposome and Montanide ISA51 VG) to treat breast, ovarian and prostate cancer
NCT01376505	I	To determine the safety and effectiveness of vaccination combining two chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B Cell Peptides emulsified in ISA 720 and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors (including ovarian cancer)
NCT01416038	I/II	To determine the safety and immunogenicity profiles of DPX-Survivac, designed to target Survivin, with a regimen of low dose oral cyclophosphamide in the treatment of ovarian, fallopian tube and peritoneal cancers
NCT01522820	I	To determine the safety and immunogenicity of the DEC-205-NY-ESO-1 fusion protein vaccine, with and without sirolimus (an mTOR inhibitor), in patients with NY-ESO-1 expressing solid tumors (including ovarian)
NCT01526473	I	To determine the safety and immunogenicity of HER2 VRP (AVX901) in patients with advanced or metastatic malignancies that express HER2 (including ovarian)
NCT01312389	I/II	To determine the feasibility, safety and immunogenicity of OC-L, an autologous vaccine comprised of autologous Oxidized tumor Cell Lysates (OC-L) administered by intradermal/subcutaneous injection in combination with Ampligen, a Toll-like receptor 3 agonist
Monoclonal Antibody
NCT00034138	I/II	To compare the safety, immunity and pharmokinetic profile of OvaRex mAb-B43.13 (oregovomab) ascites fluid product and OvaRex mAb-B43.13 cell culture product in a patients with Stage III/IV epithelial ovarian cancer
NCT00034372	II	To compare the time to disease relapse of patients who demonstrate an immune response to OvaRex mAb-B43.13 (Oregovomab) with time to disease relapse of those who do not demonstrate an immune response to OvaRex mAb-B43.13
NCT00086632	II	To determine if oregovomab received during front-line chemotherapy for ovarian cancer can create anti-tumor immune responses and thus provide a survival benefit
NCT00050375	III	To compare the time to disease relapse between post chemotherapy consolidation with oregovomab (OvaRex® mAb-B43.13) or placebo in women with ovarian, tubal or peritoneal cancer.
Cellular Immunotherapy
NCT00003887	II	To study the effectiveness of donated white blood cells in treating patients who have relapsed cancer (including ovarian cancer) following allogeneic transplantation of donated bone marrow or peripheral stem cells
NCT00004604	I	To study the effectiveness of carcinoembryonic antigen (CEA) antigen RNA-pulsed autologous DC cancer vaccine in treating patients who have metastatic cancer (including ovarian cancer) that has not responded to prior treatment
NCT00005956	I	To study the effectiveness of HER2/Neu Intracellular Doman (ICD) Protein-pulsed, Autologous, Cultured DCs followed by autologous DC mixed with tetanus toxoid (TT) and autologous DC mixed with keyhole limpet hemocyanin (KLH) in Patients with no evidence of disease after standard treatment for HER2/Neu Expressing Malignancies (including ovarian cancer)
NCT00027534	I	To study the effectiveness of autologous DCs infected with recombinant fowlpox-CEA-TRICOM vaccine in patients with advanced or metastatic malignancies expressing CEA (including ovarian cancer)
NCT00101257	I	To study the side effects and best dose of Autologous CD4+ Antigen-Specific T cells following in vitro stimulation with NY-ESO-1 pulsed DCs in patients with stage III or stage IV EOC or PPC
NCT01456065	I	To determine the safety of active immunotherapy with fully mature, Telomerase Reverse Transcriptase-mRNA and Survivin peptide double loaded DCs (Procure®) in patient with advanced ovarian cancer, enrolled within 12 weeks after completing primary therapy
NCT00603460	I II	To determine the feasibility and safety of administering vaccine-primed, ex vivo CD3/CD28-costimulated autologous peripheral blood T cells in combination with DCVax-L vaccination, following lymphodepletion with high dose cyclophosphamide/fludarabine. To assess the distribution of progression-free survival at 6 mo for patients treated with maintenance DCVax-L vaccination plus oral metronomic cyclophosphamide as well as patients treated with ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells after lymphodepletion with high dose cyclophosphamide / fludarabine, followed by DCVax-L boost vaccination and metronomic oral cyclophosphamide.
NCT01132014	0	To determine the feasibility, safety and immunogenicity of OC-DC, an autologous vaccine comprised of autologous dendritic cells (DC), administered intranodally alone or in combination with either intravenous Daclizumab or with a combination of Daclizumab and intravenous Bevacizumab.
NCT00703105	II	To determine if immunoregulatory T-cell inhibition by Ontak followed by the administration of an autologous tumor lysate-loaded dendritic cell vaccine enhances the immune response in patients with relapsed/refractory ovarian cancer
NCT00683241	I	To determine the feasibility and safety of administering DCVax-L intradermally combined with intravenous bevacizumab and oral metronomic cyclophosphamide in patients with recurrent ovarian or primary peritoneal cancer
Combination/Other
NCT00194714	I/II	To determine the safety and efficacy of monthly HER2/Neu Specific Cytotoxic T Cell vaccination in patients with HER2 overexpressing Stage IV breast and ovarian cancer who are on maintenance trastuzumab alone after being treated with chemotherapy and trastuzumab or trastuzumab alone
NCT00004021	II	Evaluate the efficacy of immunotherapy with irradiated autologous tumor cell vaccine and sargramostim (GM-CSF) followed by monoclonal antibody OKT3- activated T lymphocytes and interleukin-2 in combination with standard therapy in terms of response rate in patients with stage III or IV ovarian cancer
NCT00496860	I	To evaluate the safety, determine the maximum-tolerated dose (MTD) and characterize the pharmacokinetic profile of ALT-801(a biologic compound compose of IL-2 genetically fused to a human soluble T-cell receptor directed against p53) in previously treated patients with progressive metastatic malignancies, including ovarian cancer
NCT01384253	I	To determine the toxicity profile of intraperitoneal ^212Pb-TCMC-Trastuzumab infusion, its dose-limiting toxicities, and its anti-tumor effects in patients with HER-2 positive intraperitoneal cancers
NCT00019084	II	To study the effectiveness of tumor specific mutated p53 or Ras peptides alone or in combination with cellular immunotherapy with peptide activated lymphocytes (PALs) along with subcutaneous IL-2 in treating patients who have advanced cancer (including ovarian cancer)

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