*4.2.3.1 Manufacturing*

The technical issues are related to the manufacturing process of adoptive cellular material and the delivery platforms which also account for the success or failure of the ACT. During the *ex-vivo* expansion and genetic modification process, factors such as cell culture time, use of cytokines and use of vectors for gene transfer are the major concerns deciding the efficacy and survival of T cells being used in the therapy. Besides sometimes cancer specific T cells may not grow that well and not sufficient for infusion. At the same time efficacy of T cell may also change in *ex-vivo* growth conditions [55].

Major hurdle with regard to TCR T cell technology is related to its expansion which includes identifying of a good target, along with specific TCRs, screening for desirable TCR affinity. Also, TCR T cell therapy is MHC dependent and there is grave peril of hybridization between exogenous and endogenous chain causing recognition of auto-antigens thereby leading to graft-versus host disease [43].

Failures of the therapy with adverse outcomes have been reported due to some chromosomal DNA translocations and rearrangements during the preparation of the cells [56, 57].
