Enhancement of anti-tumor efficacy of immune checkpoint blockade by alpha-TEA

Abstract

Cancer immunotherapy such as anti-PD-1/anti-PD-L1 immune checkpoint blockade (ICB) can provide significant clinical benefit in patients with advanced malignancies. However, most patients eventually develop progressive disease, thus necessitating additional therapeutic options. We have developed a novel agent, a-TEA-LS, that selectively induces tumor cell death while sparing healthy tissues, leading to increased activation of tumor-reactive T cells and tumor regression. In the current study, we explored the impact of combined a-TEA-LS + ICB in orthotopic and spontaneously arising murine models of mammary carcinoma. We found that a-TEA-LS + ICB led to increased production of pro-inflammatory cytokines that were associated with a reduction in tumor growth and prolonged survival. Together, these data demonstrate the potential utility of a-TEA-LS + ICB for the treatment of breast cancer and provide the rationale for clinical translation of this novel approach.

Tissue biomarkers of immune checkpoint inhibitor therapy

“…Alpha‐tocopheryloxyacetic specifically causes tumor cell death while preserving healthy tissues. The study revealed that the combined therapy of alpha‐tocopheryloxyacetic and PD‐1 resulted in improved survival as well as reduced tumor size (86%), compared with 13% in the IgG group, 27% in the alpha‐tocopheryloxyacetic group and 17% in the PD‐1 group of control 42 . Moreover, recent work showed that the stimulator of interferon genes (STING) pathway introduces a new approach of biodegradable nanoparticles (NP1 and NP2) using a PC7A‐based polymer to encapsulate chemotherapeutic platinum complexes.…”

“…The study revealed that the combined therapy of alphatocopheryloxyacetic and PD-1 resulted in improved survival as well as reduced tumor size (86%), compared with 13% in the IgG group, 27% in the alphatocopheryloxyacetic group and 17% in the PD-1 group of control. 42 Moreover, recent work showed that the stimulator of interferon genes (STING) pathway introduces a new approach of biodegradable nanoparticles (NP1 and NP2) using a PC7A-based polymer to encapsulate chemotherapeutic platinum complexes. These nanoparticles are designed to enhance chemotherapy and immunotherapy through the activation of the STING pathway involving both DNA fragmentation/cyclic GMP-AMP synthase activation and PC7A binding.…”