Objective clinical regression of metastatic breast cancer in disparate sites after use of whole-cell vaccine genetically modified to release sargramostim.
A patient with recurrent breast cancer metastases following initial response to chemotherapy and hormonal maintenance was treated with a whole-cell tumor vaccine, resulting in a prompt objective complete remission of a lung lesion on computed tomography (CT) scans and near-complete regression of multiple breast lesions on magnetic resonance imaging (MRI). Three months after completion of the protocol, metastases were again found in the breast and lung, with new lesions in the brain and liver. Reinstitution of vaccine inoculation resulted in major regression of the brain and breast lesions, improvement in all other areas, and no indication of new lesions. Therapy consisted of inoculation of 20 x 10(6) SV-BR-1-GM cells, a unique breast cancer cell line transfected to release sargramostim (granulocyte macrophage colony-stimulating factor [GM-CSF]). Following lethal irradiation to 200 cGy, vaccine was injected intradermally in four divided doses to the back and thighs, every 2 weeks x 3, then every month x 3. Each treatment was preceded 48 hours earlier with low-dose cyclophosphamide 300 mg/m2 to abrogate regulatory T-cell activity. Interferon (IFN)-alpha, 20,000 IU, was injected into each inoculation site at 48 and 96 hours postinoculation to provide an additional "danger signal." The patient developed positive delayed-type hypersensitivity responses and also antibody reactivity to the vaccine cells.
Wiseman
Charles L
CL
Immunotherapy Laboratory, St Vincent Medical Center, Los Angeles, CA 90057, USA. clwmd@aol.com
Kharazi
Alex
A
D000912:Antibodies, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D018270:Carcinoma, Ductal, Breast / Q000556:secondary / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D017698:Postmenopause; D011994:Recombinant Proteins; D014057:Tomography, X-Ray Computed
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007155:Immunologic Factors; D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor