Tumor-specific recombinant idiotype immunisation after chemotherapy as initial treatment for follicular non-Hodgkin lymphoma.
Tumor-specific variable regions of the clonal immunoglobulin (idiotype, Id) expressed by B cell non-Hodgkin lymphoma (NHL) can be targeted by active immunotherapy. We conducted a phase I/II trial to determine the safety and immunogenicity of a patient-specific, recombinant, mammalian cell-derived Id protein conjugated to keyhole limpet hemocyanin (Id-KLH; MyVax personalised immunotherapy) in 22 patients with follicular NHL in first remission after chemotherapy. Subjects received five subcutaneous immunisations with MyVax plus locally administered granulocyte-macrophage colony-stimulating factor (GM-CSF). Among 21 evaluable patients, 62% mounted Id-specific immune responses. Evoked anti-Id antibodies recognised both recombinant Id and native Id, and could specifically stain autologous tumor cells. At median follow-up of more than 6 years, median progression-free survival is 38 months. Immunisation of follicular lymphoma patients with MyVax Id-KLH is safe and patients often mount tumor-specific immune responses. These results form the basis of a pivotal phase 3 trial of MyVax in follicular NHL.
Timmerman
John M
JM
Division of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA. jtimmerman@mednet.ucla.edu
Vose
Julie M
JM
Czerwinski
Debra K
DK
Weng
Wen-Kai
WK
Ingolia
Diane
D
Mayo
Martha
M
Denney
Dan W
DW
Levy
Ronald
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D007167:Immunotherapy / Q000009:adverse effects; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D011994:Recombinant Proteins