Yu Baofa, Han Yan, Fu Qiang, Gao Feng, Jing Peng, Guoqin Zheng, Zhang Peicheng, Huang Jianbo, Zhang Jian
Jinan Baofa Cancer hospital, Jinan, Shandong Province, China, 250000.
Beijing Baofa Cancer Hospital, Beijing, China, 100010.
J Cancer. 2023 May 8;14(8):1282-1292. doi: 10.7150/jca.82985. eCollection 2023.
Intratumoral immunotherapy is well studied and is ongoing, but few studies have evaluated the relationship between of cytotoxic drugs intratumoral injection (CDI) and hapten-enhanced cytotoxic drugs intratumoral injection (HECDI) and patient survival. The objectives of this study include comparisons to explore possible associations between the proportions of treatment-induced cytokines and autologous antibodies to tumor-associated antigens (TAAs) and the relative size of the abscopal effects concurring. CDIs contain oxidant and cytotoxic drugs, HECDIs contains the same drug plus penicillin as the new Hapten. Of the 33 patients with advanced pancreatic cancer, 9 received CDI, 20 received HECDI, and 4 (control group) received placebo. Serum levels of cytokines and autoantibodies of TAAs were detected and compared after therapy. The 1-year survival rate was 11.11% for CDI and 52.63% for HECDI (P= 0.035). In the general analysis of cytokines, HECDI exhibited an increasing level of IFN-γ and IL-4, and the non-hapten CDI showed a rising level of IL-12 (P = 0.125, 0.607, & 0.04). Participants who did not receive chemotherapy had significant differences in the level of Zeta autoantibody only before and after HECDI; However, IMP1 levels in patients with previous chemotherapy experience were significantly different before and after HECDI and CDI treatment (P≤0.05, P = 0.316). After HECDI treatment, TAA autoantibodies of RalA, Zeta, HCC1, p16 increased (P = 0.429, 0.416, 0.042, 0.112). The elevated levels of CXCL8, IFN-γ, HCC1, RalA, Zeta, and p16 observed in HECDI may be attributed to the abscopal effect (P = 0.012 & 0.013). Overall survival rates indicated that HECDI treatment extended participants' lives.
瘤内免疫疗法已得到充分研究且仍在进行中，但很少有研究评估细胞毒性药物瘤内注射（CDI）和半抗原增强细胞毒性药物瘤内注射（HECDI）与患者生存率之间的关系。本研究的目的包括进行比较，以探索治疗诱导的细胞因子比例和肿瘤相关抗原（TAA）的自体抗体与同时出现的远隔效应的相对大小之间可能存在的关联。CDI包含氧化剂和细胞毒性药物，HECDI包含相同的药物加青霉素作为新的半抗原。在33例晚期胰腺癌患者中，9例接受CDI，20例接受HECDI，4例（对照组）接受安慰剂。治疗后检测并比较细胞因子和TAA自体抗体的血清水平。CDI组的1年生存率为11.11%，HECDI组为52.63%（P = 0.035）。在细胞因子的总体分析中，HECDI显示IFN-γ和IL-4水平升高，非半抗原CDI显示IL-12水平升高（P = 0.125、0.607和0.04）。未接受化疗的参与者仅在HECDI治疗前后Zeta自体抗体水平有显著差异；然而，有化疗经验的患者在HECDI和CDI治疗前后IMP1水平有显著差异（P≤0.05，P = 0.316）。HECDI治疗后，RalA、Zeta、HCC1、p16的TAA自体抗体增加（P = 0.429、0.416、0.042、0.112）。在HECDI中观察到的CXCL8、IFN-γ、HCC1、RalA、Zeta和p16水平升高可能归因于远隔效应（P = 0.012和0.013）。总体生存率表明HECDI治疗延长了参与者的生命。
