Multi-epitope T-cell Vaccine Shows Promise in Ovarian, Breast Cancer

Article

TPIV200 stimulates T cells to attack ovarian and triple-negative breast tumor cells that over-express the folate receptor alpha protein.

Clinicians in the not-too-distant future may have something new to offer women with breast cancer and ovarian cancer in whom initial therapy fails to yield a response. Writing in Clinical Cancer Research, investigators at the Mayo Clinic report that a vaccine is showing benefit in combating ovarian cancer in women who have suffered recurrence following successful platinum-based therapy.

In a phase I study, patients were immunized over a 6-month period following pretreatment with cyclophosphamide, and then monitored for an additional 12 months. Investigators found that the TPIV200 vaccine generated robust immune responses and was well tolerated by all patients. There was only one Grade 3 adverse event reported in the study, and it was related to a local ulceration that resolved.

TPIV200 is a multi-epitope T-cell vaccine that targets folate receptor alpha (FRa). It is comprised of a mixture of five folate receptor alpha peptides. “These are mixed with an adjuvant or immune-stimulant (GM-CSF [granulocyte-macrophage colony-stimulating factor]) to give the drug product which is injected into patients. The mechanism of action is to broadly stimulate T cells to attack tumor cells (ovarian and triple-negative breast) that overexpress the folate receptor alpha protein. The peptides were chosen to cover about 90% of the population,” said Richard Kenney, MD, Acting Chief Medical Officer for TapImmune, Jacksonville, Florida.

The study showed that generation of T-cell immunity following immunization was robust and long-lasting. Analysis showed 91% of patients had an antigen-specific response, with 89% of those patients responding to multiple epitopes included in TPIV200. The researchers reported that T-cell responses developed slowly over the course of vaccination. In this initial study, the median time to maximal immunity was 5 months. Ovarian cancer patients, who entered the study upon their first remission (n = 10) had a median progression-free survival (PFS) of 528 days (95% CI, 110–548 days).

TapImmune, Inc., which is developing this vaccine in partnership with the Mayo Clinic and Sloan-Kettering Cancer Center, believes this vaccine product could eventually help a significant number of women who now have few treatment options. Peter Hoang, President and CEO of TapImmune, said all patients remained alive at last follow-up, at least 2 years following initiation of immunization. He said the observed median PFS of 528 days is an interesting result because the historical data with patients receiving standard-of-care therapy in this setting show a median PFS of 313 days. 

The current phase I study enrolled women with histologically confirmed stage II–III breast cancer or stage II–IV ovarian (including primary peritoneal and fallopian tube) cancer who had completed systematic therapy (except for hormonal treatment or bisphosphonates) at least 90 days prior to registration. All the women were without evidence of disease at time of enrollment. Dr. Kenny noted that women in first remission are likely to have healthier immune systems, having not gone through multiple rounds of chemotherapy. He said this may better position them to benefit from vaccination with TPIV200. 

                                                                      

 

 

 

 

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