The expression “adoptive cell transfer” (ACT) is commonly employed to indicate

The expression “adoptive cell transfer” (ACT) is commonly employed to indicate an immunotherapeutic regimen involving the isolation of autologous blood-borne or tumor-infiltrating lymphocytes their selection/expansion/activation ex vivo and their reinfusion into the patient most often in the context of lymphodepleting pre-conditioning and in combination with immunostimulatory treatments. of ever more efficient and safer ACT protocols. Accordingly the number of clinical trials testing ACT in oncological indications does not cease to increase. In this Trial Watch we summarize recent developments in this exciting area of research covering both high-impact studies that have been published during the last 12 months and clinical trials that have been launched in the same period to evaluate the safety and therapeutic potential of ACT in cancer patients. avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2 best known as HER2) 172 173 in patients bearing HER2+ solid neoplasms (“type”:”clinical-trial” attrs :”text”:”NCT01935843″ term_id :”NCT01935843″NCT01935843); (5) autologous T lymphocytes expressing a CAR specific for epidermal growth factor receptor (EGFR) 174 175 in Edg3 subjects with advanced EGFR+ malignancies (“type”:”clinical-trial” attrs :”text”:”NCT01869166″ term_id :”NCT01869166″NCT01869166); and (6) autologous PBLs genetically modified to express a NY-ESO-1-targeting TCR in subjects affected by metastatic NY-ESO-1+ tumors (“type”:”clinical-trial” attrs :”text”:”NCT01967823″ term_id :”NCT01967823″NCT01967823). As for the clinical trials listed in our previous Trial Watches dealing with this topic 75 76 the following studies have changed status during the past 12 mo: “type”:”clinical-trial” attrs :”text”:”NCT01236573″ term_id :”NCT01236573″NCT01236573 now listed GSK1070916 as “Suspended”; “type”:”clinical-trial” attrs :”text”:”NCT00871481″ term_id :”NCT00871481″NCT00871481 now listed as “Completed”; as well as “type”:”clinical-trial” attrs :”text”:”NCT01555892″ term_id :”NCT01555892″NCT01555892 “type”:”clinical-trial” attrs :”text”:”NCT01567891″ term_id :”NCT01567891″NCT01567891 “type”:”clinical-trial” attrs :”text”:”NCT01653717″ term_id :”NCT01653717″NCT01653717 “type”:”clinical-trial” attrs :”text”:”NCT01729091″ term_id :”NCT01729091″NCT01729091 and GSK1070916 “type”:”clinical-trial” attrs :”text”:”NCT01758458″ term_id :”NCT01758458″NCT01758458 now listed as “Recruiting.” Nor the reasons underlying the suspension of “type”:”clinical-trial” attrs :”text”:”NCT01236573″ term_id :”NCT01236573″NCT01236573 testing IL-12-expressing TILs combined with ipilimumab in metastatic melanoma patients nor the results of “type”:”clinical-trial” attrs :”text”:”NCT00871481″ term_id :”NCT00871481″NCT00871481 investigating the therapeutic profile of NY-ESO-1-redirected TILs combined with IL-2 and ipilimumab in a similar setting appear to be available (source http://www.clinicaltrials.gov). In summary the enthusiasm that has gathered GSK1070916 around ACT-based immunotherapy throughout the past 2 decades remains high. The use of autologous CAR-expressing T lymphocytes for the treatment of B-cell neoplasms or genetically unmodified TILs for the therapy of melanoma stand out as the protocols of this type most intensively evaluated in the clinics today. Concluding Remarks Accumulating evidence suggests that ACT-based anticancer immunotherapy may soon cease to be a promising experimental regimen and become an established clinical reality. This said the 2 2 treatment-related deaths recorded by Morgan and colleagues upon the infusion of autologous T cells expressing a GSK1070916 MAGE-A3-targeting CAR6 101 should warn the scientific and medical community about the potential downsides of this approach. As for many other TAA-specific immunotherapeutic regimens including DNA-based as well as peptide-based vaccines 176 177 the efficacy as well as the safety of ACT-based interventions relying on genetically engineered T cells depends on the TAA of choice.178 Strategies based on the simultaneous targeting of 2 distinct TAAs are being actively investigated not only as they would be associated with limited on-target toxicity for normal tissues that express one single TAA but also as they may limit the surge of antigen-loss tumor variants.119 179 180 Moreover the safety and efficacy of ACT-based immunotherapeutic regimens relying on genetically manipulated T lymphocytes appear to depend on the affinity and avidity of exogenously introduced TAA receptors be them TCRs or CARs.102 103 181 Significant efforts have been dedicated at the development of 2nd and 3rd generation CARs that deliver potent immunostimulatory cues to T cells de facto bypassing the need for.