Finding suitable targets is the major obstacle to cancer gene therapy

摘要

The durable complete cancer regressions observed in patientswith metastatic melanoma receiving adoptive cell transfer (ACT)has demonstrated the power of this cell transfer approach forthe treatment of cancer.1 The administration of autologous tumor-in?ltrating lymphocytes (TILs) along with interleukin-2 following alymphodepleting preparative regimen can lead to durable cancerregressions in 20–40% of patients with metastatic melanoma,most of whom were refractory to established regimens.2Thus, attempts to develop lymphocytes with antitumor activityhave become a major effortin studies of current cancerimmunotherapy. The identi?cation of naturally occurring cellswith antitumor activity, for use in ACT, has thus far been limited toa small subgroup of cancers. Although TIL can be grown fromvirtually any cancer deposit, melanomas appear unique in theability to reproducibly give rise to large numbers of cells withantitumor activity that can be readily detected by in-vitro assays.In-vitro sensitization of lymphocytes with tumor antigens can giverise to cells with antitumor activity, though successful examples ofthe use of these cells in the human are few.In an effort togenerate antitumor lymphocytes for use in ACT in humans,attention has thus been turned to the genetic modi?cation ofnormal circulating lymphocytes with retroviruses encoding eitherconventional alpha/beta T cellreceptors (TCRs) or chimericantigen receptors (CARs) that can recognize cancers.