On September 22, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported that its research partner, Helmholtz Munich, presented preclinical data showing that Phio’s lead clinical product PH-762, an INTASYL compound targeting PD-1, increases the T cell population expressing stem cell-like characteristics, which in doing so, is expected to improve T cell persistence in vivo, therefore, resulting in enhanced duration of anti-tumor activity (Press release, Phio Pharmaceuticals, SEP 22, 2022, View Source [SID1234621354]). These data were presented at the 9th Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (ITOC) annual meeting, which is being held September 22 to 24, 2022 in Munich, Germany.
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"A well-known hurdle in adoptive cell therapy (ACT) with T cells is the poor persistence of effector T cells in patients, which are key players in killing tumor cells. These data demonstrate that PH-762 enhances the population of T cells that have more stem-like characteristics. As has been reported in literature, stem-like T cells are more resilient and result in an ACT product with prolonged tumor killing activity," said Dr. Simon Fricker, Phio’s VP of Research and Development. "Increasing the frequency of this cell population by downregulating PD-1 using our PH-762 INTASYL compound is expected to enhance the population of T cells that fight cancer by increasing their proliferative activity, persistence, responsiveness and cell differentiation – characteristics that are believed to improve the immune system’s capacity to kill cancer cells."
"These new data complement the robust data set we’ve generated over the past several years for PH-762 in the treatment of melanoma by reducing the expression of PD-1, a clinically validated target for immunotherapy. Currently, Phio is conducting a first-in-human clinical trial of PH-762 to treat patients with advanced melanoma," concluded Dr. Fricker.
This preclinical study assessed the potential of PH-762 to downregulate PD-1 to increase the frequency of a CD8 T cell population with a stem-like associated marker profile. T cells were incubated with PH-762 and co-cultured with an autologous renal cell carcinoma tumor cell line. Results showed that PH-762 treatment reduced PD-1 surface expression in T cells compared to control and PH-762 mediated PD-1 silencing increased the population of T cells that expressed stem-like markers, including higher expression levels of certain surface markers that identify stem cell memory T cells.
ITOC is a European meeting providing a global platform for translational research in the field of immuno-oncology as well as a forum for discussion of early clinical translation and to address its unique challenges. The presentation detailing these data is titled, "RNAi mediated PD-1 knockdown induces a TCF-1 positive population in activated human CD8 T cells with stem-like associated marker profile."
About PH-762
PH-762 activates immune cells to better recognize and kill cancer cells by reducing the expression of PD-1, a clinically validated target for immunotherapy. PD-1 is expressed by T cells and prevents them from killing cancer cells. When PH-762 reduces PD-1 expression, the "brakes" on the immune system are released and T cells are activated to kill the cancer cells. PH-762 is being developed as a standalone drug therapy with local intratumoral administration. In addition, it is also being developed as a critical component of cellular immunotherapy, more specifically, to improve tumor cell killing capability of adoptively transferred tumor infiltrating lymphocyte (TIL) therapy.