A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma.
The study objectives were to determine; (1) whether activated T cells could be generated from peripheral blood of patients immunized with their own cancer cells, (2) whether adoptive transfer of the activated T cells to patients had toxic effects and (3) whether the infused cells produced clinical responses. Study patients had recurrent, surgically accessible grade III/IV astrocytomas. The patients were tapered off steroids after total surgical resection and immunized with autologous cancer cells plus Bacillus, Calmette and Guerin (BCG). Peripheral blood mononuclear cells were activated with anti-CD3, expanded with interleukin-2 (IL-2) and reinfused to patients. The number of activated T cells that was given back to patients varied between 10(10) and 10(11). Side effects that were observed following immunization and adoptive cell transfer included mainly transient flu-like symptoms. One patient's tumor partially regressed, but there was no effect on survival. Two other patients' tumors regressed, and the patients are apparently disease-free more than 5 and 4 years later. The other six patients' tumors were apparently unaffected by the treatment. Patient age, tumor grade and CD4/CD8 composition of infused cells were positively correlated with clinical responses. Cellular immunotherapy is feasible and is associated with minimal toxicity. Additional appropriately controlled studies will be required to determine whether cellular immunotherapy could be used as a treatment for central nervous system malignancy. Additional studies also will be required to determine the underlying immunological mechanisms.
Wood
G W
GW
Department of Pathology, University of Kansas Medical Center, Kansas City, USA. gwood@kc.rr.com
Holladay
F P
FP
Turner
T
T
Wang
Y Y
YY
Chiga
M
M
D000276:Adjuvants, Immunologic; D000328:Adult; D001500:BCG Vaccine; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D016516:CD4-CD8 Ratio; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007117:Immunization, Secondary; D016233:Immunotherapy, Active / Q000009:adverse effects; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000528:radiation effects; D010865:Pilot Projects; D012074:Remission Induction; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D019496:Cancer Vaccines; D016853:Muromonab-CD3