Cd7-KO Mouse

Cd7, an antigen belonging to the immunoglobulin superfamily, is expressed on the surface of all thymocytes, most mature T cells, and natural killer cells. It has proposed functions in T-cell activation and intercellular adhesiveness [4].

In the context of T-cell malignancies, CD7 is a transmembrane protein highly expressed in acute T-cell leukemia (T-ALL) and some peripheral T-cell lymphomas. Targeting CD7 with chimeric antigen receptor (CAR) T cells has been explored, but the major challenge is CAR T-cell fratricide due to CD7 expression on both normal and malignant cells. Strategies like genetic manipulations to ablate the CD7 gene [1], using protein expression blockers to downregulate CD7 [3], or pharmacologic inhibition of key CAR/CD3ζ signaling kinases [2] have been employed to overcome this. For instance, CD7-edited T cells can expand without compromising cytotoxic function against malignant T-cell lines and primary tumors in mouse xenograft models of T-ALL [1].

In conclusion, Cd7 is significant in T-cell biology. Its high expression in T-cell malignancies makes it a potential target for immunotherapy. However, the issue of fratricide in CD7-targeted CAR T-cell therapy has been a major hurdle. Studies using gene-editing techniques, similar to gene knockout approaches, have been crucial in understanding how to overcome this and develop effective treatments for T-cell malignancies [1,2,3].

References:

1. Gomes-Silva, Diogo, Srinivasan, Madhuwanti, Sharma, Sandhya, Brenner, Malcolm K, Mamonkin, Maksim. 2017. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. In Blood, 130, 285-296. doi:10.1182/blood-2017-01-761320. https://pubmed.ncbi.nlm.nih.gov/28539325/

2. Watanabe, Norihiro, Mo, Feiyan, Zheng, Rong, Brenner, Malcolm K, Mamonkin, Maksim. 2022. Feasibility and preclinical efficacy of CD7-unedited CD7 CAR T cells for T cell malignancies. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 24-34. doi:10.1016/j.ymthe.2022.09.003. https://pubmed.ncbi.nlm.nih.gov/36086817/

3. Png, Yi Tian, Vinanica, Natasha, Kamiya, Takahiro, Coustan-Smith, Elaine, Campana, Dario. 2017. Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. In Blood advances, 1, 2348-2360. doi:10.1182/bloodadvances.2017009928. https://pubmed.ncbi.nlm.nih.gov/29296885/

4. Haftcheshmeh, Saeed Mohammadian, Tajbakhsh, Amir, Kazemi, Mohaddese, Fazeli, Mostafa, Sahebkar, Amirhossein. 2018. The clinical importance of CD4+ CD7- in human diseases. In Journal of cellular physiology, 234, 1179-1189. doi:10.1002/jcp.27099. https://pubmed.ncbi.nlm.nih.gov/30067877/