Transimmunization for cutaneous T cell lymphoma: a Phase I study.
Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma (CTCL). It involves four sequential steps: conversion of blood monocytes into dendritic antigen presenting cells (DC) by repetitive adherence and disadherence to plastic surface; reinfusion of the new DC; presumed in vivo loading of the new DC with apoptotic malignant leukocytes; and expansion of the anti-tumor CD8 T cell pool. To assess the safety of a methodology designed to increase ex vivo contact between the apoptotic malignant cells and new DC prior to reinfusion, a single-center, open-label Phase I clinical study of a revised procedure--referred to as "Transimmunization"--was conducted in CTCL patients. Twenty-seven subjects were treated monthly for 3 to 5 months, alone or in combination with electron beam therapy. For those receiving Transimmunization alone, there was an overall diminution in infiltrative lesions in eleven (55%) of twenty patients. In the twelve leukemic CTCL patients, there was a significant mean reduction of 50.1% in the circulating malignant cells, as determined with family-specific anti-T cell receptor Vbeta monoclonal antibodies (P <or= 0.021). Because this therapy permits the synchronous induction and tumor loading of DC, with minimal toxicity, Transimmunization may merit further investigation in CTCL and other malignancies.
Girardi
Michael
M
Department of Dermatology, Yale University School of Medicine, CT 06520-8059, USA. girardi@yale.edu
Berger
Carole L
CL
Wilson
Lynn D
LD
Christensen
Inger R
IR
Thompson
Kacie R
KR
Glusac
Earl J
EJ
Edelson
Richard L
RL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D018929:Cell Culture Techniques; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016410:Lymphoma, T-Cell, Cutaneous / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating; D017893:Photopheresis; D016896:Treatment Outcome