产生治疗性单克隆抗体 NEO-201,源自癌症疫苗,针对人类恶性肿瘤和免疫抑制细胞。
Generation of the therapeutic monoclonal antibody NEO-201, derived from a cancer vaccine, which targets human malignancies and immune suppressor cells.
发表日期:2024 Aug 26
作者:
Massimo Fantini, Kwong Y Tsang, Philip M Arlen
来源:
Cellular & Molecular Immunology
摘要:
癌症疫苗刺激激活针对癌细胞的特异性体液和细胞适应性反应。可以分离并进一步选择疫苗接种后产生的抗体,以开发针对肿瘤相关抗原的高度特异性和有效的单克隆抗体(mAb)。这篇综述描述了不同类型的癌症疫苗、Hollinshead 癌症疫苗平台产生 mAb NEO-201 的过程、NEO-201 识别的抗原的表征、NEO-201 结合并介导杀死癌细胞和免疫抑制细胞的能力( gMDSCs和Tregs)通过ADCC和CDC,NEO-201临床前和临床毒性和疗效。为了克服癌症疫苗临床疗效差的问题,由于免疫抑制细胞的活性,癌症疫苗可以与其他能够消耗细胞毒性的免疫治疗药物联合使用免疫抑制细胞。单独使用 NEO-201 或与派姆单抗联合使用 NEO-201 的临床试验结果表明,治疗后疾病的持久稳定是由于 NEO-201 能够靶向并降低循环 Tregs 和 gMDSC 的百分比。这些发现提供了令人信服的支持将 NEO-201 与癌症疫苗结合起来,重新整合它们引发针对癌症的强大而持久的免疫适应性反应的能力。
Cancer vaccines stimulate the activation of specific humoral and cellular adaptive responses against cancer cells.Antibodies generated post vaccination can be isolated and further selected to develop highly specific and potent monoclonal antibodies (mAbs) against tumor-associated antigens.This review describes different types of cancer vaccines, the process of the generation of the mAb NEO-201 from the Hollinshead cancer vaccine platform, the characterization of the antigen recognized by NEO-201, the ability of NEO-201 to bind and mediate the killing of cancer cells and immunosuppressive cells (gMDSCs and Tregs) through ADCC and CDC, NEO-201 preclinical and clinical toxicity and efficacy.To overcome the problem of poor clinical efficacy of cancer vaccines, due to the activity of immunosuppressive cells, cancer vaccines could be combined with other immunotherapeutics able to deplete immunosuppressive cells. Results from clinical trials, employing NEO-201 alone or in combination with pembrolizumab, showed that durable stabilization of disease after treatment was due to the ability of NEO-201 to target and reduce the percentage of circulating Tregs and gMDSCs.These findings provide compelling support to combine NEO-201 with cancer vaccines to reintegrate their ability to elicit a robust and durable immune adaptive response against cancer.