full free access: Journal of Hematology & Oncology - Ovarian cancer immunotherapy: opportunities, progresses and challenges

"Abstract

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer.(see tables 2 & 3)
We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer." (see more for tables 2 & 3)

Table 2

Findings from Clinical Trials of Immunotherapy for Ovarian Cancer
Strategies	Phase	Immune response	Clinical response	Reference
Antibody-based vaccine
Anti-CA125 (Oregovomab MAb B43.13)	I/II	Increased Ag specific T cells	Improved survival	[25,26,75,76]
Anti-idiotype Ab (ACA-125)	I/II	Induced Ab3, Ab1 and ADCC of CA125+ tumor cells	Improved survival	[28,77]
Anti-HER-2 (trastuzumab, pertuzumab)	I/II	NR*	Stable disease for more than 2.5 months	[78,79]
Anti-MUC-1 idiotypic Ab (HMFG1)	I/II	Induced Humoral Immune Responses	Prolonged survival	[80,81]
Peptide vaccine
HER2/neu	I/II	Developed humoral and T cell immune Response	NR*	[13,14]
NY-ESO-1	I	Induced both humoral and cellular immune responses	NR*	[82,83]
Cytokine vaccine
IL-2	I/II	NR*	Prolonged survival	[84]
IFN-α	I/II	NR*	20% complete and 8% partial response	[85-87]
IFN-γ	I	Increased cytotoxity against tumor associated macrophages	NR*	[32,88,89]
Tumor cell vaccine
Whole tumor cells	I	CD8 T-cell response	No clinical response	[33]
Tumor cells transfected with GM-CSF	I	NR*	Improve survival	[34]
Dendritic cell vaccine
DC pulse with autologous tumor antigen	I	DTH	NR*	[90]
DC pulse with mRNA of FR-α		CD4+ and CD8+ T-cell responses	NR*	[91]
DC/tumour-fusion vaccine	Pre-clinical trial	Elevated serum levels of ANA	NR*	[92]
DC pulse with peptide	Pre-clinical trial	CTL	NR*	[43]
HSP vaccine
Gp96	I	Increased NK cell activity		[unpublished data]
* Not reported
Liu et al. Journal of Hematology & Oncology 2010 3:7   doi:10.1186/1756-8722-3-7

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Table 3

Summary of the Strengths and Limitations of Ovarian Cancer Immunotherapy
Strategies	Pros	Cons
Antibody-based vaccine	Tumor antigen specific. Easy to produce.	Weak immunogenicity. Not for all individuals.
Peptide vaccine	Safe, stable, and easy to produce and modify.	Poor immunogenicity. HLA restriction.
Cytokine vaccine	Easy to manufacture and administer.	Non-specific immunomodulating only.
Tumor cell vaccine	Convenience, contained tumor antigen pool.	Potential safety concern. Difficult to produce. Difficult to standardize.
Dendritic cell vaccine	Powerful professional antigen presenting cells. May prime both T cells and antibody response.	Difficult to manufacture and standardize.
HSP vaccine	May contain multiple antigens.	Difficult to manufacture and standardize.
Immunomodulation with Treg blockage	Promising strategy	No data on ovarian cancer yet Difficult to completely eliminate Treg.
Liu et al. Journal of Hematology & Oncology 2010 3:7   doi:10.1186/1756-8722-3-7