Preliminary report on tumor stem cell/B cell hybridoma vaccine for recurrent glioblastoma multiforme.
BACKGROUND
Glioblastoma multiforme (GBM), the most aggressive glioma, presents with a rapid evolution and relapse within the first year, which is attributed to the persistence of tumor stem cells (TSC) and the escape of immune surveillance. Mixed leukocyte culture (MLC) cytoimplant has been shown to function as a powerful intratumor pro-inflammatory cytokine pump. Tumor B-cell hybridoma (TBH) vaccines have been shown to function as antigen-presenting cells. We evaluated the toxicity and efficiency of each treatment alone and in combination.


METHODS
In an open study, 12 consecutive patients were evenly divided into 3 groups, each group receiving 3 different treatments. Patients in Group 1 were treated, after diagnosis, with debulking surgery (DS)+radiotherapy (Rx), and after the first relapse underwent DS+MLC treatment. Patients in Group 2 were similarly treated but after the first relapse underwent DS+MLC+TBH. Finally, patients in Group 3 were similarly treated but after the first relapse underwent DS+TBH. Nestin PAP stain assessed TSC participation in TBH.


RESULTS
Treatment with MLC had strong and rapid therapeutic effects, but was limited in duration and induced various degrees of brain inflammation. Treatment with MLC+TBH acted synergistically, provoking a rapid, strong and lasting therapeutic response but also generating different degrees of brain inflammation. A lasting therapeutic effect without generating high degrees of brain inflammation occurred in patients treated with TBH vaccine alone.


CONCLUSIONS
TSC vaccine consisting of TBH alone seems to have potent adjuvant reactions overcoming both persistence of tumor stem cells and immune escape of GBM without provoking an encephalitic reaction.
Moviglia
Gustavo A
GA
Fundación Regina Mater, Buenos Aires, Argentina. gmoviglia@reginamater.com
Carrizo
Antonio G
AG
Varela
Gabriela
G
Gaeta
Carlos A
CA
Paes de Lima
Andrea
A
Farina
Pablo
P
Molina
Hugo
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000637:transplantation*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000637:transplantation*
D019496:Cancer Vaccines