Interstitial transfer factor as adjuvant immunotherapy for experimental glioma.
Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells which transmit the ability to express delayed-type hypersensitivity and cell mediated immunity from sensitized donors to nonimmnune recipients. In this study, we determined the efficacy of TF as immunotherapy to treat experimental glioblastoma. We used TF obtained from immunized swine. We evaluated different doses of intratumoral TF (product of 4x10(6), 8x10(5) and 1.6x10(5) cells). The best dose (product of 4x10(6) cells) of TF was also combined with carmustine for experimental therapy in rats with C6 malignant glioma. Modifications in peripheral blood T lymphocyte counts ( CD2+, CD4+, CD8+ and NK) were evaluated by flow cytometry. Cytokine expression in the tumour was assessed by RT-PCR and apoptosis was evaluated using the sub G0 method. Intratumoral TF reduced significantly the tumour size, and increased CD2+, CD4+, CD8+ and NK cell counts, it also increased the percentage of apoptotic tumour cells and the percentage of tumour tissue expressing Th1 cytokines. We observed an additive antitumoral effect when TF was combined with chemotherapy.
Neuroimmunology Unit, National Institute of Neurology and Neurosurgery of Mexico, Mexico City. benpio76@hotmail.com
B
B
Pineda
S
S
Estrada-Parra
B
B
Pedraza-Medina
A
A
Rodriguez-Ropon
R
R
Pérez
O
O
Arrieta
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002330:Carmustine / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000187:drug effects; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014165:Transfer Factor / Q000627:therapeutic use*
D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D014165:Transfer Factor; D002330:Carmustine