Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, United States.
Veana Therapeutics, Portland, OR, United States.
Front Immunol. 2023 Feb 22;14:1057702. doi: 10.3389/fimmu.2023.1057702. eCollection 2023.
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.
癌症免疫疗法，如抗 PD-1/抗 PD-L1 免疫检查点阻断（ICB），可以为晚期恶性肿瘤患者提供显著的临床获益。然而，大多数患者最终会出现疾病进展，因此需要额外的治疗选择。我们开发了一种新型药物 a-TEA-LS，它选择性地诱导肿瘤细胞死亡，同时保护健康组织，从而增加肿瘤反应性 T 细胞的激活和肿瘤消退。在本研究中，我们探讨了 a-TEA-LS+ICB 在原位和自发发生的乳腺癌小鼠模型中的影响。我们发现，a-TEA-LS+ICB 导致促炎细胞因子的产生增加，与肿瘤生长减少和生存时间延长相关。总之，这些数据表明 a-TEA-LS+ICB 治疗乳腺癌的潜力，并为这种新方法的临床转化提供了依据。
