Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor- specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 μg, 150 μg, 500 μg, or 1500 μg total peptide mixed with 100 μg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation (3H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 1012 leukemia cells. (C) 2000 by The American Society of Hematology.

PINILLA-IBARZ, J., Cathcart, K., Korontsvit, T., Soignet, S., Bocchia, M., Caggiano, J., et al. (2000). Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. BLOOD, 95(5), 1781-1787 [10.1182/blood.v95.5.1781.005k46_1781_1787].

Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses

BOCCHIA M.;
2000-01-01

Abstract

Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor- specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 μg, 150 μg, 500 μg, or 1500 μg total peptide mixed with 100 μg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation (3H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 1012 leukemia cells. (C) 2000 by The American Society of Hematology.
2000
PINILLA-IBARZ, J., Cathcart, K., Korontsvit, T., Soignet, S., Bocchia, M., Caggiano, J., et al. (2000). Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. BLOOD, 95(5), 1781-1787 [10.1182/blood.v95.5.1781.005k46_1781_1787].
File in questo prodotto:
File Dimensione Formato  
85935_UPLOAD.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 177.37 kB
Formato Adobe PDF
177.37 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/3944
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo