Leukemia and Lymphoma

Caring Cross is developing a multi-targeted chimeric antigen receptor T-cell immunotherapy for leukemia and lymphoma. The TriCAR-T cell immunotherapy is designed to address relapse that can occur when patients with Leukemia or Lymphoma are treated with a single targeting anti-CD19 CAR T-cell product.

Approximately 50% of patients treated with a single anti-CD19 CAR-T cell therapy relapse due to loss of the CD19 epitope that the CAR binds to kill the tumor cell.  To prevent relapse due to loss of the CD19 epitope, the targeting multiple surface proteins on the tumor may significantly decrease the chance of relapse. Previousl studies have shown that dual targeting of both CD19 and CD20 leads to higher complete rates in Lymphoma (Shah et al., Nature Medicine, 2020).  CD22 is a surface protein common on Leukemia cells and a single anti-CD22 CARs have been successfully used to treat leukemia (Fry et al. 2018) .  Therefore, our   TriCAR  that targets CD19, CD20 and CD22could lead to higher complete remission rates for both Leukemia and Lymphoma.

We are partnering with Academic Medical Centers and Government Agencies to clinically develop and bring to regulatory approval TriCAR-T cell immunotherapy. To learn more about these partnerships, please contact [email protected].

Two proof of concept studies showing the promise of targeting CD19, CD20 and CD22 are shown here below:

Schneider D, Xiong Y, Wu D, Hu P, Alabanza L, Steimle B, Mahmud H, Anthony-Gonda K, Krueger W, Zhu Z, Dimitrov DS, Orentas RJ, Dropulić B. Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Sci Transl Med. 2021 Mar 24;13(586):eabc6401. doi: 10.1126/scitranslmed.abc6401. PMID: 33762438.

Fousek K, Watanabe J, Joseph SK, et al. CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression. Leukemia. 2021;35(1):75-89. doi:10.1038/s41375-020-0792-2

Reference:

Shah, N. et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies; a phase 1 dose escalation and expansion trial. Nature Medicine. 2020; 26, 1569-1575. 

Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24(1):20-28. doi:10.1038/nm.4441