Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma.
Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.
Eton
O
O
Department of Melanoma/Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Kharkevitch
D D
DD
Gianan
M A
MA
Ross
M I
MI
Itoh
K
K
Pride
M W
MW
Donawho
C
C
Buzaid
A C
AC
Mansfield
P F
PF
Lee
J E
JE
Legha
S S
SS
Plager
C
C
Papadopoulos
N E
NE
Bedikian
A Y
AY
Benjamin
R S
RS
Balch
C M
CM
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D001859:Bone Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D019496:Cancer Vaccines; D003598:Cytoskeletal Proteins / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D007110:Immunity, Active; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000276:immunology / Q000628:therapy; D015996:Survival Rate; D013997:Time Factors; D014466:Ultraviolet Rays
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019496:Cancer Vaccines; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D007074:Immunoglobulin G; D008050:Lipid A; C112124:detox adjuvant