Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a phase I trial in metastatic melanoma.
OBJECTIVE
We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with a T-cell receptor encoding gene.


METHODS
Cells were administered intratumorally in four dose levels ranging from 10(8) to 10(9) cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles.


RESULTS
Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient.


CONCLUSIONS
Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.
Department of Oncology , Aarhus University Hospital, Denmark. duval@as.aaa.dk
Lone
L
Duval
Henrik
H
Schmidt
Keld
K
Kaltoft
Kirsten
K
Fode
Jens Jorgen
JJ
Jensen
Steen Mellerup
SM
Sorensen
Michael I
MI
Nishimura
Hans
H
von der Maase
D000328:Adult; D000951:Antigens, Neoplasm; D002460:Cell Line; D005221:Fatigue / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005334:Fever / Q000209:etiology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009363:Neoplasm Proteins / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell