Biomedical subjects

C M Richman

Publications and source records attributed to C M Richman.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Prolonged cryopreservation of human granulocytes.

Normal human granulocytes prepared by dextran sedimentation were cryopreserved in 10 percent dimethyl sulfoxide and 25 percent autologous plasma using controlled-rate freezing at -1 degrees C per minute. Twenty-four samples were stored from 0 to 8 months in the vapor or liquid phase of liquid nitrogen. The mean cell recovery was 58 +/- 4 percent and the mean bactericidal activity using Staphylococcus aureus was 72 +/- 4 percent. Cells stored for approximately 5 months examined with transmission electron microscopy had intact cell membranes and granules although some nuclear changes were observed. No decline in cell recovery or bactericidal activity was observed with prolonged storage and there was no advantage of liquid over vapor phase. Samples stored for over 8 months showed a 73 percent cell recovery and a 77 percent bactericidal activity. Maintenance of granulocyte function after prolonged cryopreservation in these studies suggests the feasibility of cryopreserved granulocyte transfusion therapy.

Adult↗

PubMedDate not supplied

Yttrium-90/indium-111-DOTA-peptide-chimeric L6: pharmacokinetics, dosimetry and initial results in patients with incurable breast cancer.

BACKGROUND: Radioimmunotherapy (RIT) using 131I-Chimeric L6 (ChL6) antibody has shown therapeutic promise for patients with breast cancer. To enhance this potential, a novel immunoconjugate was developed that targets adenocarcinomas like breast cancer and tightly binds yttrium-90 (90Y) for therapy and indium-111 (111In) for imaging. The radioimmunoconjugate consists of a macrocyclic chelator (DOTA) linked to ChL6 by a catabolizable peptide. 90Y-DOTA-peptide-ChL6 was designed to minimize the radiation dose to critical normal tissues, thereby improving the therapeutic index. MATERIALS AND METHODS: Three patients with incurable metastatic breast cancer received 90Y/111In-DOTA-peptide-ChL6 for 5 pharmacokinetics/dosimetry studies and one of these patients also received 2 therapy doses. Quantitative imaging of 111In and in vitro assay of 90Y and 111In in blood urine and bone marrow samples were obtained. RESULTS: 90Y/111In-DOTA-peptide-ChL6 was prepared at high purity and was stable in vivo. Assays of bone marrow revealed no evidence for escape of 90Y or 111In from the chelate. 111In imaging of tumors was excellent, providing a therapeutic index for tumor to marrow radiation as high as 229 to 1. 90Y and 111In provided comparable pharmacokinetics, as did tracer and therapeutic doses of radioimmunoconjugates. One patients that received 2 therapeutic doses of 90Y-DOTA-peptide-ChL6 showed regression of tumors and tumor markers. Toxicities were relatively minor and no anti-globulin response developed despite 5 immunoconjugate infusions. CONCLUSIONS: This first study in patients of radioimmunoconjugates with a catabolizable linker between the metal chelator and the antibody confirmed that these novel 90Y/111In-DOTA-peptide-ChL6 radioimmunoconjugates have significant potential. Tracer doses of 111In-DOTA-peptide-ChL6 for imaging predicted the behavior of therapeutic doses of 90Y-DOTA-peptide-ChL6. The latter radioimmunoconjugate induced regression of tumors and tumor markers without significant toxicity. When compared to earlier 131I-ChL6 dosimetry, 90Y-DOTA-peptide-ChL6 provided a therapeutic index several times better.

Antibodies, Monoclonal↗

PubMedDate not supplied

Radioimmunotherapy for advanced breast cancer using I-131-ChL6 antibody.

BACKGROUND: The biologically active, antiadenocarcinoma monoclonal antibody chimeric L6 (ChL6) was labeled with 131I and administered in cycles to patients with metastatic breast cancer who had failed standard therapy. The therapeutic potential, tumor targeting and maximum tolerated dose of 131I-ChL6 were studied. METHODS: Ten patients with L6 reactive breast cancer received an imaging dose of 131I-ChL6 followed 24 hours later by a therapy dose of 131I-ChL6 (20-70 mCi/m2). Patients received up to 4 monthly cycles unless they had significant myelosuppression, progression of disease, or a high human anti-mouse antibody titer. In vivo activation of effector cell function, complement levels and cytokine release were studied. RESULTS: All 10 patients had detectable cancer on the imaging study. In 7 patients with superficial cancer, the radiation dose was 120 to 3700 cGy/cycle; 5-30 times higher than the whole body dose. Therapy resulted in minimal acute or subacute toxicity. Dose limiting toxicities were neutropenia and thrombocytopenia. Six of 10 patients had clinically measurable tumor responses; 5 had responses that lasted more than one month (1.5-5 months). The MTD for 131I-ChL6, given in at least two monthly doses, was 60 mCi/m2. CONCLUSION: Objective clinical responses were seen in five of 10 patients treated with 131I-ChL6. The tumor response in heavily pretreated, advanced breast cancer may be related to the combined effects of targeted radiation and the biological activity of L6/ChL6.

Adenocarcinoma↗

PubMedDate not supplied

Synergistic therapy of breast cancer with Y-90-chimeric L6 and paclitaxel in the xenografted mouse model: development of a clinical protocol.

BACKGROUND: Paclitaxel (Taxol) has demonstrated synergistic enhancement of radioimmunotherapy (RIT) of breast cancer with Y-90 labeled antibody ChL6, in the xenografted mouse model. To determine the optimal sequence and timing of RIT and Taxol for a prospective clinical trial, efficacy and dosimetry in mice, and dosimetry in patients receiving RIT alone, were examined. MATERIALS AND METHODS: Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 microCi), and i.p. Taxol (300 or 600 micrograms) 72, 48, or 24 hours prior to RIT, or 6, 24, 48, or 72 hours after RIT. RESULTS: Taxol after RIT resulted in cure, CR, or PR of all mice (70/70 tumors) and demonstrated greater therapeutic enhancement (p = 0.001) than Taxol before RIT. Mice receiving 600 micrograms Taxol 48 hours after RIT achieved 88% cure (7/8 tumors). In mice, 57% and 42% of the radiation dose to tumor and marrow, respectively, was delivered from 48-336 hours after RIT; in patients receiving 90Y-DOTA-peptide-ChL6, the corresponding values were 56% and 22%. CONCLUSIONS: Taxol given approximately 48 hours after RIT provides coincident peak deposition of Taxol and Y-90 in tumor, and no Taxol in the marrow during the major radiation dose to marrow, resulting in therapeutic enhancement without observable additive toxicity. A clinical trial of low dose Taxol given after RIT to patients with metastatic breast cancer is planned.

Adenocarcinoma↗