The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results from a study of the human papillomavirus 16 (HPV16)-specific synthetic long peptide therapeutic vaccine, ISA101, administered in combination with carboplatin/paclitaxel chemotherapy in patients with HPV16-positive advanced or recurrent cervical cancer showed that overall survival (OS) was significantly prolonged in patients with an HPV16-specific T cell immune response to ISA101. The findings from this study were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.1

Previous research involving the administration of ISA101 monotherapy to patients with premalignant HPV-induced anogenital cancers has shown durable complete remissions in approximately half of treated patients. However, in the setting of cancer, T-cell activation, expansion, and effector functions are suppressed by myeloid cell populations, regulatory T cells, and the expression of coinhibitory molecules. A prior study demonstrated a normalization of immune suppressive myeloid cells and stronger tumor immunity induced by ISA101 when the treatment vaccine was coadministered with chemotherapy.

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In this nonrandomized, dose-assessment study (ClinicalTrials.gov Identifier: NCT02128126), 4 doses of the ISA101 (20, 40, 100 and 300 µg per peptide) with or without immunomodulator pegylated interferon alpha, were coadministered with standard-dose carboplatin/paclitaxel chemotherapy to patients with HPV-positive advanced or recurrent cervical cancer who had no curative treatment options.

Of the 72 patients evaluable for objective regression, the rate was 43%.  Among 61 patients tested, depletion of suppressive myeloid cells with chemotherapy was associated with low-level spontaneous HPV16-specific immunity in 26 patients. Type 1 T-cell responses to ISA101 were observed across all dosage cohorts, with no significant differences seen in strength of response as it related to vaccine dose. 

A key finding of the study was that OS in patients receiving any dose of ISA101 with a HPV16-specific T cell immune response to ISA101 that was above the median, as measured by a validated interferon gamma enzyme-linked immunospot (IFNγ-ELISpot) assay,was significantly longer compared with those with a lower HPV-specific immune responses (16.8 months vs 11.2 months; log-rank P =.012). This finding was independent of differences in general immune status. 

“Our study demonstrates that chemo-immunotherapy can be exploited to the benefit of patients with cervical cancer and warrants confirmation of the benefit of this type of chemo-immunotherapy in a randomized controlled study in HPV16-induced cancer patients,” the authors noted in conclusion. 

Disclosure: The presenters have disclosed financial ties to ISA Pharmaceuticals. For a full list of disclosures, please see the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.

References

  1. Melief CJM, Welters MJP, Vergote I, et al. A strong HPV-specific T-cell response after chemoimmunotherapy for advanced cervical cancer is associated with prolonged survival. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract CT002. 
  2. Cole GA. Interferon-gamma ELISPOT assay for the quantitative measurement of antigen-specific murine CD8+ T-cells. Methods Mol Biol. 2005;302:191-204.