Car T Cells Solid Tumours

Car t cell therapy is emerging as a promising approach to redirect t cells from cancer patients into tumor specific killer cells ex vivo 1 2 this technology has yielded effects in some patients.

Car t cells solid tumours. However this success has yet to be extrapolated to solid tumors and the reasons for this are being actively investigated. Recent studies have shown that hpse deficiency in in vitro. Chimeric antigen receptor car t cells have been strikingly successful in the treatment of hematologic cancers 1 but have not been effective against solid tumors thus far. The use of dual car designs that recognize multiple antigens at once and local administration of car t cells are both strategies that have been used to overcome the hurdle of localization to the tumor.

While car t cells engineered to fight cancer have shown promise for curing childhood leukemia in clinical trials at seattle children s solid tumors pose unique challenges. To date car t cells have demonstrated tremendous success in eradicating hematologic malignancies e g cd19 cars in leukemias. Adoptive cell therapy using car t cells has emerged as a novel treatment strategy with promising results against b cell malignancies. Car t cells have been less effective against solid tumours 3 4 5 in part because they enter a hyporesponsive exhausted or dysfunctional state 6 7 8 9 triggered by chronic antigen.

Details of t cell therapy research at king s college targeting solid tumors and hematological cancers. Beyond these t cell intrinsic properties a complex and dynamic immunosuppressive tumor microenvironment in solid tumors hinders t cell efficacy. These car t cells are engineered to express synthetic receptors that redirect polyclonal t cells to surface antigens for subsequent tumor elimination. However car t cells have not shown much success against solid malignancies.

Many cars are designed with elements that augment t cell persistence and activity. Therefore car t cells attacking solid tumors must be able to degrade hspgs by releasing heparanase hpse to access tumor cells. Several known obstacles to car t cell therapy for solid tumors include target antigen identification effective trafficking to the tumor robust activation proliferation and in vivo cytotoxicity. The unique challenges posed to car t cell therapy by solid tumors can be described in three steps.

Solid tumors exist in protective microenvironments that help them evade the immune system making it more difficult to keep the car t cells stimulated. There are several obstacles which diminish the efficacy of car t cells but the immunosup.