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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 673-683
Idiotype Vaccination in Human Myeloma: Generation of Tumor-Specific
Immune Responses After High-Dose Chemotherapy
Massimo Massaia,
Paolo Borrione,
Silvano Battaglio,
Sara Mariani,
Eloise Beggiato,
Patrizia Napoli,
Claudia Voena,
Alberto Bianchi,
Marta Coscia,
Barbara Besostri,
Silvia Peola,
Thomas Stiefel,
Jos Even,
Domenico Novero,
Mario Boccadoro, and
Alessandro Pileri
From the Divisione di Ematologia and II Servizio di Anatomia
Patologica dell'Universita' di Torino, Azienda Ospedaliera San
Giovanni Battista di Torino, Torino, Italy; Biosyn Arzeittemel,
Fellbach, Germany; and INSERM U277/Department d'Immunologie Institut
Pasteur, Paris, France.
Igs contain unique portions, collectively termed idiotypes (Id),
that can be recognized by the immune system. Id expressed by tumor
cells in B-cell malignancies can be regarded as tumor-specific antigens
and a target for vaccine immunotherapy. We have started a vaccination
trial in multiple myeloma (MM) using Id-specific proteins conjugated to
keyhole limpet hemocyanin (KLH) as immunogens and low doses of
subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF)
or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had
previously been treated with high-dose chemotherapy followed by
peripheral blood progenitor cell (PBPC) transplantation entered this
study from August 1995 to January 1998. All patients were in first
remission at the time of vaccination. They received subcutaneous
injections of Id vaccines and immunoadjuvants in an outpatient setting.
The generation of Id-specific T-cell proliferative responses was
documented in 2 patients, whereas a positive Id-specific delayed-type
hypersensitivity (DTH) reaction was observed in 8 of the 10 patients
studied. DTH specificity was confirmed in 1 patient by investigating
the reactivity to synthetic peptides derived from the VDJ sequence of
the tumor-specific Ig heavy chain. None of the patients generated
soluble immune responses to Id, whereas the generation of soluble and
cellular immune responses to KLH was observed in 100% and 80%,
respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from
disease progression (FFDP), measured from the date of first Id/KLH
injection to the date of first treatment after vaccination or last
follow-up, ranged from 9 to 36 months. These data indicate that the
immune competence status of MM patients is still susceptible to
specific immunization after high-dose chemotherapy and PBPC
transplantation. It remains to be determined whether generation of
Id-specific immune responses can reduce the relapse rate of patients
with minimal residual disease.
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