Realism and pragmatism in developing an effective chimeric antigen receptor T-cell product for solid cancers.
Over the last two decades, harnessing the power of the immune system has shown substantial promise. Specifically, the successes that chimeric antigen receptor (CAR) T cells achieved in the treatment of hematologic malignancies provided a concrete platform for further development in solid tumors. Considering that the latter contribute more than three quarters of cancer-related deaths in humans makes it clear that solid tumors represent the larger medical challenge, but also the larger developmental promise in the market. In solid tumors though, the more is achieved the more challenges are unveiled. The mere fact that engineered T cells are personalized therapies rather than a mass product has been a main constraint for clinical outspread. Further, the complexity of the hostile solid tumor microenvironment, antigenic diversity and dynamicity and the presence of a tenacious stem cell population rendered the effective development to the clinic questionable. In this article we shed light on the importance of a realistic understanding of challenges faced in solid tumors and some very innovative efforts to overcome these challenges in a manner that paves a pragmatic yet realistic road toward effective development at the discovery level and beyond.
Basic Research Department, Children's Cancer Hospital Egypt 57357, Cairo, Egypt; Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt. Electronic address: ahmed.z.gad@aucegypt.edu.
Ahmed Z
AZ
Gad
Basic Research Department, Children's Cancer Hospital Egypt 57357, Cairo, Egypt.
Shahenda
S
El-Naggar
Basic Research Department, Children's Cancer Hospital Egypt 57357, Cairo, Egypt; Center for Cell and Gene Therapy, Baylor College of Medicine and Houston Methodist Hospital, Houston, Texas, USA; Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA. Electronic address: nahmed@bcm.edu.
Nabil
N
Ahmed
D000818:Animals; D005818:Genetic Engineering; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000191:economics; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D011948:Receptors, Antigen, T-Cell
T cells; chimeric antigen receptors; immune escape; immunotherapy; solid tumor; tumor-associated antigens