At the 2022 annual meeting of the American Association for Cancer Research (AACR), BioNTech released its phase 1 clinical data of CAR-T + CARVac in the treatment of Claudin6 (CLDN6) positive solid tumors (testicular cancer, ovarian cancer, etc.). Among the 14 patients who can evaluate the efficacy, the objective remission rate was 43%, and the disease control rate was 86%, showing good safety and encouraging preliminary therapeutic effects. This is also the first human trial to improve the expansion and persistence of CAR-T cells with mRNA vaccines.

However, at the latest European Society of Oncology (ESCO), BioNTech presented the new clinical trial results, which showed that of the 21 patients currently assessable, the objective remission rate dropped to 33% and the disease control rate dropped to 67%.

CAR T-cell therapy has completely changed the treatment choice of hematological malignant tumors, but its application in solid tumors has always been a challenge. One of the major limitations is that most therapeutic targets on solid tumors are also expressed in small amounts in normal cells, which makes it difficult to target CAR T-cell s specifically to tumor cells without harming normal cells. In addition, the inhibitory tumor microenvironment of solid tumor makes it difficult for CAR T-cell s to last and CAR T-cell s to penetrate solid tumor.

This open-label, multicenter human clinical trial aims to evaluate the safety and preliminary efficacy of CLDN6-CAR-T cell therapy (BNT211). CLDN6 is a tumor-specific antigen widely expressed in a variety of solid tumors but silenced in normal adult tissues.

In January 2020, the preclinical study published by BioNTech in Science showed that the combination of CLDN-CAR-T and mRNA vaccine encoding CLDN6 could promote the expansion of CAR T-cell s and increase their persistence, thus improving the lethality to tumors.

According to the newly released data, a total of 22 patients received the treatment, including 13 patients with testicular cancer, 4 patients with ovarian cancer, 1 patient with endometrial cancer, 1 patient with fallopian cancer, 1 patient with sarcoma and 1 patient with gastric cancer, and 1 patient with cancer of unknown origin. Of the 21 assessable cancer patients, the objective remission rate (ORR) was 33%, and the vacancy rate was 67%, of which 1 was in complete remission, 6 in partial remission, and 7 in stable condition. This is similar to the data released at the AACR conference in April, but the effect has declined.

It is worth mentioning that the therapeutic effect of this therapy on 7 patients with testicular cancer is encouraging, of which 1 is in complete remission, 3 in partial remission, and 2 in stable condition. The objective remission rate (ORR) was 57% and the disease control rate was 85%.

In terms of safety, only one patient had grade 3 cytokine release syndrome and one patient had transient grade 1 neurotoxicity. These two adverse events were resolved quickly. This indicates that CLDN6-CAR-T therapy and combination therapy with CARVac are safe, and only limited and controllable adverse events occur.

These data show that CLDN6-CAR-T cell therapy alone and CLDN-CAR-T + CAR-Vac combination therapy are safe and show promising therapeutic effects for CLDN6-positive cancer patients.

Prior to this, CLDN6 has not been used as a target for cell therapy, and this clinical trial shows that cell therapy targeted by CLDN6 is more effective in the treatment of solid tumors.