Introduction
Historical Perspective: Is Cancer Immunogenic?
Antigen category | Antigens | Tumor type | Vaccine | Reference |
---|---|---|---|---|
Differentiation Antigens | Tyrosinase | Melanoma | Yes | Int J Cancer 1996;67:54[60] |
Melan- Mart-1 | Melanoma | Yes | Cancer J Sci Am 1997; 3:37[61] | |
gp-100 | Melanoma | Yes | Nat Med 1998; 4:321[62] | |
Overexpression/Amplification | HER-2/neu | Ovarian cancer Breast cancer | Yes | J Clin Oncol. 2002; 20:2624[13] |
Antigens | p53 | various tumors | Yes | J Immunol 1998; 160:328[63] Cancer Immunol Immunother. 2004; 53:633[64] |
Mutational Antigens | p53 | various tumors | Yes | J Clin Oncol 2005; 23:5099[65] |
Ras | various tumors | Yes | Int J Cancer 2001; 92:441[66] | |
Cancer Testis Antigens | MAGE | Melanoma | Yes | Int J Cancer 1999; 80:219[67] |
NY-ESO-1 | Ovarian cancer | Yes | Clin Cancer Res. 2008; 14:2740[31] | |
LAGE-1 | Ovarian cancer Melanoma Bladder cancer | No | Cancer Res. 2003; 63:6076[20] | |
Glycolipid Antigens | MUC-1 | Adenocarcinoma | Yes | J. Clin. Invest. 1997; 100:2783[68] |
MUC-16 (CA125) | Ovarian cancer | Yes | Int J Cancer 2002; 98:737[69] Clin Cancer Res. 2004; 22:3507[70] | |
Oncofetal Antigens | AFP | Germ cell tumors | No | Gynecol. Oncol. 2000; 77:203[71] |
CEA | Colorectal cancer | Yes | Ann Surg Oncol 1996; 3:495[72] | |
PSA | Prostate cancer | Yes | Urology 1999; 53:260[73] | |
Viral Antigens | HPV | Cervical cancer | Yes | Lancet 1996; 347:1523[74] |
Clinical Evidence for the Role of Immunosurveillance Against Human Ovarian Cancer
Intratumoral T cells correlate with clinical outcome
Predictable value of tumor infiltrating regulatory T cells
Ovarian Cancer Immunotherapy as an Effective Treatment Modality: The Hypothesis
Clinical Trials of Immunotherapeutic Strategies Against Ovarian Cancer: the Opportunities
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 | |
Anti-idiotype Ab (ACA-125) | I/II | Induced Ab3, Ab1 and ADCC of CA125+ tumor cells | Improved survival | |
Anti-HER-2 (trastuzumab, pertuzumab) | I/II | NR* | Stable disease for more than 2.5 months | |
Anti-MUC-1 idiotypic Ab (HMFG1) | I/II | Induced Humoral Immune Responses | Prolonged survival | |
Peptide vaccine
| ||||
HER2/neu | I/II | Developed humoral and T cell immune Response | NR* | |
NY-ESO-1 | I | Induced both humoral and cellular immune responses | NR* | |
Cytokine vaccine
| ||||
IL-2 | I/II | NR* | Prolonged survival | [84] |
IFN-α | I/II | NR* | 20% complete and 8% partial response | |
IFN-γ | I | Increased cytotoxity against tumor associated macrophages | NR* | |
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] |
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. |