Vaccination + Chemotherapy Associated with Prolonged Cancer Survival

ISA101 vaccination during chemotherapy in cervical cancer patients regressed tumors
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(Vax Before Cancer)

Despite advances in prevention and early detection, cervical cancer remains a worldwide health issue, causing needless mortality in women.

In general, the immune system of patients with late-stage cancer is compromised to such an extent that vaccine monotherapy generally fails.

However, there is good news regarding therapeutic cancer vaccines inducing regressions of premalignant oncogenic Human Papillomavirus type 16 (HPV16) induced anogenital lesions.

HPV16 the predominant HPV type causing oropharyngeal cancers.

But, according to a study published on March 16, 2020, the treatment of HPV16-induced cancers requires innovative countermeasures to overcome cancer-induced immune suppression.

This small study shows the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. 

Tumor regressions were observed in 43 percent of 72 evaluable patients in this study.

And, the group of 32 patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve, when compared to the 32 patients with lower than median induced HPV-specific immune responses. 

This difference was not explained by pre-existing HPV16-specific immunity or the general immunocompetence of T cells, because the reactivity to unrelated microbial antigens was similar in both groups.

This finding demonstrates that chemo-immunotherapy can be exploited to help patients with advanced HPV cancer, based on a defined mode of action.

This was a multicenter, open-label nonrandomized phase 1/2 study with expansion cohorts to determine the safety and immunomodulating effects of the therapeutic HPV16 E6/E7 SLP vaccine (ISA101) as immunotherapy in combination with standard-of-care chemotherapy (carboplatin and paclitaxel) in women with HPV16-positive advanced (FIGO stage IIIb-IVa with the involvement of lymph nodes beyond the renal vein), metastatic (FIGO stage IVb), or recurrent cervical cancer.

This study comes with 2 important limitations. 

These researchers from the Netherlands were not able to collect pre- and post-vaccination tumor material, the study of which may have allowed us to determine the myeloid cell–depleting effect in the tumor microenvironment as well as the presence of T cell infiltration and particular therapy-induced changes in that compartment. 

The new data support the findings from a 2009 study published in JAMA by the same researchers showing that the vaccine led to clinical responses in 60 percent of patients with HPV-related cervical or vulvar premalignant lesions.

The researchers disclosed various industry relationships.

HPV vaccine development news published by Vax-Before-Cancer.