Racotumomab (1E10), a Monoclonal Anti-Idiotype Tumor Vaccine Against N-Glycolyl-Containing Gangliosides

MARIANO R. GABRI; MÓNICA CASTRO; YILDIAN DÍAZ; ADDYS GONZÁLEZ; MARCELO D. GUTHMANN; ARMANDO LÓPEZ; SAILY ALFONSO; EDUARDO SANTIESTEBAN; AMPARO MACÍAS; EDUARDO SUÁREZ; DANIEL E. GÓMEZ; ROBERTO E. GÓMEZ; LEONARDO FAINBOIM; ENRIQUE MONTERO; GABRIELA CINAT; ROLANDO PÉREZ; DANIEL F. ALONSO; ANA MARÍA VÁZQUEZ

Atenas, Grecia

Workshop; Recent Advances in Cancer Immunotherapy with an Emphasis on Vaccines; 2008

European Society of Cancer Immunology and Immunotherapy

Ganglioside molecules have become an attractive target for immunotherapy in cancer. N-glycolyl gangliosides are acidic glycolipids not expressed in normal human tissues but overexpressed in solid tumors as breast cancer. Racotumomab is a monoclonal antibody (mAb) generated by immunizing BALB/c mice with an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides. Nineteen patients with high-risk (stage II and III) or metastatic breast cancer were vaccinated with different dose levels of Racotumomab (0.5, 1, and 2 mg). Racotumomab was able to develop a strong sera specific antibody response against NgGM3 ganglioside and self tumor specimen. Additionally, we assessed the involvement of T cells in the anti-idiotypic response and observed the induction of IFNg secretion in 5 of 13 evaluable patients (J Immunother 2006;29:215). To explore the potential antitumor activity of Racotumomab as a cancer vaccine in lung cancer, preclinical experiments in mice were done. C57BL/6 mice were challenged with Lewis lung carcinoma cells (3LL-D122) and treated with Racotumomab showing a significantly reduced incidence of lung metastasis. Antitumor effect was associated with a substantial reduction of new blood vessel formation in tumors and an induction of apoptosis in metastatic tissues. Analyzing a panel of human lung cancer samples, we observed by antibody mediated stain, the positive expression of NgGM3 in Non-Small Lung Cancer (NSCLC) (13/16) (81%). In an open study based on a compassionate-use, 71 patients stage IIIb and stage IV NSCLC patients were treated with Racotumomab, after receive standard chemotherapy and radiotherapy. No evidence of serious adverse effects was reported. Median survival time of the patients who entered the study with partial response or disease stabilization and with a PS1 after the first line of chemo/radiotherapy was 11. 5 months from starting vaccination. When these patients were compared to a historical control matched group the difference between median survival time was significative (11.5 vs 5.7 months) (P