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Biomedical subjects

M V Pimm

Publications and source records attributed to M V Pimm.

At least 109 records · Page 6Linked to original sources
PubMed1984

Experience in the preparation and experimental use of immunocytostatics.

Vindesine (VDS) was coupled directly to a monoclonal antibody (791T/36) raised against a human osteogenic sarcoma cell line, and methotrexate (MTX) was coupled to 791T/36 via an intervening human serum albumin (HSA) bridge. Both the VDS-791T/36 and MTX-HSA-791T/36 conjugates were cytotoxic in vitro specifically for tumour target cells expressing the 791T/36-defined antigen, while the free drug in each case was indiscriminately toxic to all target cells. The VDS-791T/36 conjugate retarded growth of osteogenic sarcoma xenografts in immunodeprived mice when administered in multiple doses. Free 791T/36 did not significantly affect tumour growth. VDS was tumour inhibitory, but was toxic to the mice at a total dose of 20 micrograms per kg body weight, while VDS-791T/36 conjugate was not toxic at total doses incorporating VDS at up to 45 mg per kg. It is suggested that this is due to selectivity conferred upon the conjugate by the antibody moiety, and that such conjugates may offer considerable potential as anti-cancer agents.

Animals↗
PubMed1984

Immunoscintigraphy of colorectal carcinoma with monoclonal antibody 791T/36.

A monoclonal antibody 791T/36 prepared against a human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinoma by external imaging of patients infused with 131I-labelled antibody. Positive images were obtained with 8/11 primary colon tumours, 5/12 rectal tumours and 14/15 secondary and recurrent tumours. Positive tumour localization of radiolabelled antibody was confirmed by imaging and radioactivity counts on resected specimens. None of five patients with benign colorectal disease showed positive images and only 2/12 other gastrointestinal cancers were detected.

Animals↗
PubMed1983

Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting.

Developments in hybridoma technology leading to the production of monoclonal antibodies recognizing tumor-associated antigens are providing new approaches for the radioimmunodetection of, and drug targeting to, metastases. These developments are illustrated in a series of studies on the in vivo localization of an antihuman-osteogenic sarcoma monoclonal antibody (791T/36) in human tumor xenografts maintained in immunodeprived mice. 131I-labelled 791T/36 antibody localized specifically in osteogenic sarcomas but not in xenografts of other tumors, such as bladder carcinoma T24, which do not express the antigen identified by this antibody. Developing from these studies, various parameters influencing antibody localization in tumors were examined including the kinetics of antibody uptake, the relationship between tumor size and antibody binding, and the site of antibody deposition. This provides a basis for considering the potential of antitumor monoclonal antibodies for targeting antitumor agents. Of particular importance here is the observation that antibody is principally located at the periphery of tumors since this will influence the population of cells within a tumor which can be attacked by antibody-drug or antibody-toxin conjugates. Experiments with human tumor xenografts demonstrate tumor localization of radioisotope-labelled 791T/36 monoclonal antibody. Tumor localization by external gamma camera imaging of osteogenic sarcoma xenograft-bearing mice was also demonstrated. These studies illustrate the potential of antitumor monoclonal antibodies for imaging primary and metastatic tumors. This approach is further emphasized by the radioimmunodetection of primary and metastatic colorectal carcinomas.

Animals↗
PubMed1983

Interferon-alpha conjugation to human osteogenic sarcoma monoclonal antibody 791T/36.

Human lymphoblastoid interferon-alpha (IFN-alpha) has been coupled using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to a murine monoclonal antibody (791T/36) which reacts with antigens expressed on human osteogenic sarcomas. The purified conjugates retain antibody activity as defined by their capacity to compete with binding of fluorescein isothiocyanate-labelled 791T/36 antibody to 791T cells. IFN-alpha-791T/36 antibody conjugates synthesized with 125I-trace-labelled IFN-alpha and 131I-trace-labelled antibody also bound to 791T cells, but not to bladder carcinoma T24 cells. The conjugates also retain the capacity of free IFN to activate natural killer cells in human peripheral blood lymphocytes and show specific localization in human osteogenic sarcoma xenografts developing in immunodeprived mice. These findings establish that conjugates containing IFN linked to a monoclonal antibody reacting with osteogenic sarcoma-associated antigens have potential for targeted immunotherapy and in related investigations with antibody has been shown by gamma camera imaging of patients following infusion of 131I-labelled antibody to localize in primary osteogenic sarcomas.

Animals↗
PubMed1983

Localisation of human osteosarcoma by antitumour monoclonal antibody.

Immunoscintigraphy using radioisotope-labelled monoclonal antibody prepared against osteosarcoma 791T cells was used to detect a primary osteosarcoma. The eight-centimetre tumour was detected using rectilinear scintigraphy of 131I-labelled antibodies. Image enhancement was achieved by subtraction of blood-pool radioactivity labelled with technetium-99m. The ratio of tumour to non-tumour uptake of radioactivity (5:1) suggested that antibody targeting of therapeutic agents is feasible.

Adolescent↗
PubMed1983

Monoclonal antibodies for radioimmunodetection of tumours and for targeting.

A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour: non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon0. Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 antibody defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents.

Animals↗
PubMed1982

Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody.

In 10 out of 11 patients with colorectal cancer radiolabelled antitumour monoclonal antibody (791T/36) was localised to the tumour. The mean tumour to non-tumour uptake ratio of antibody demonstrated by imaging with a gamma camera was 4.4/1 after subtraction of background radioactivity. The antibody did not localise in one patient who had received radiotherapy to his tumour two weeks previously. In 5 patients with primary neoplasms localisation of the antibody was confirmed by further imaging of the resected specimens and in-vitro radioactivity counting of the tumour and comparison with the activity in adjacent normal colon.

Adult↗
PubMed1982

Cellular interactions modulating host resistance to tumours.

Active specific immunotherapy of carcinogen-induced rat tumours can be effected using vaccines containing tumour cells admixed with bacterial vaccines such as BCG and C. parvum. The nature of the tumour antigen preparation is important, the most effective immunogen being viable tumour cells whose growth is controlled by responses generated by the bacterial agent in the vaccine. Soluble tumour antigen preparations are usually ineffective due to the preferential induction of suppressor lymphocyte responses in normal hosts. In comparison, removal of suppressor precursors by cyclophosphamide treatment of animals leads to the development of tumour immunity following immunization with soluble antigen preparations. One component of the immune rejection response involves the generation of non-specific effector cells. This type of response can also be induced by administering chemical hypersensitizing agents so as to localize tumour deposits. This approach has proved highly effective in treating the guinea pig line 10 hepatoma by intralesional injection of alkylcatechols. These compounds are highly potent hypersensitizers, being the active constituents of the poison ivy/oak (urushiol oil), and localize in tumour cell membranes.

Adjuvants, Immunologic↗
PubMed1982

Complement-dependent cytotoxicity of anti-human osteogenic sarcoma monoclonal antibodies.

Two mouse monoclonal antibodies against the human osteogenic sarcoma 791T were examined for their capacity to exert complement-dependent cytotoxicity against a panel of human tumour cell lines. Cytotoxicity was most evident against the immunizing tumour 791T although significant reactivity was directed against other osteogenic sarcomas. In admixture, the 2 antibodies displayed synergism in their cytotoxicity although this was only demonstrable with defined ranges of antibody concentration. The cytotoxicity of these antibodies was dependent upon the use of rabbit serum as complement and no tumour-cell lysis was produced using human, guinea-pig or mouse serum complement. The more potent cytotoxic antibody failed to modify the outgrowth of 791T tumour xenografts in immunodeprived mice even though localization of antibody at the tumour site has been demonstrated (Pimm et al., 1982).

Animals↗
PubMed1980

Multiple antigenic specificities within primary 3-methylcholanthrene-induced rat sarcomas and metastases.

Sarcomas were induced in WAB/Not rats by subcutaneous injection of 10, 5 or 1 mg 3-methylcholanthrene (MCA) but not by 0.1 mg. Although tumours appeared earlier in rats given 10 mg MCA, compared with 1 mg, the majority of transplant lines from primary tumours were immunogenic and there was no correlation between the inducing dose of carcinogen and the growth characteristics or immunogenicities of the transplant lines. Most importantly sublines established from opposite poles of primary sarcomas were antigenically distinct in a substantial portion of cases, indicating that the primary tumours consisted of antigenically heterogeneous populations of cells. Furthermore, with one rat, renal and pulmonary metastases were antigenically distinct from a peritoneal secondary and the primary growth. These findings indicate that primary carcinogen-induced tumours may be polyclonal in origin and this has implications for both the understanding of the carcinogenic process, and for the immunotherapy of malignant disease.

Animals↗
PubMed1979

Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6'-dimycolate) and synthetic analogues.

The ability of cord factor (trehalose-6, 6'-dimycolate) and a range of shorter carbon chain fatty acid trehalose diesters to suppress growth of an ascitic rat hepatoma has been examined and compared with that of whole, living BCG organisms. Aqueous suspensions of BCG, and cord factor in 0.4% arachis oil:Triton emulsion, injected intraperitoneally, retarded growth of up to 10(5) ascites tumour cells. Trehalose-6, 6'-dibehenate was also tumour-suppressive, but only against lower challenge inocula (10(4) cells). Trehalose-6, 6'-dipalmitate and 6,6'-di-0-2-tetradecyl -3-hydroxyoctadecanoyl alpha, alpha trehalose (designated C76) were virtually ineffective and 6,6' -di-0-2-eicosyl-3-hydroxy-tetracosanoyl alpha, alpha trehalose (designated C100) gave small and variable effects only against low challenge inocula. However, improved responses were seen with light mineral oil in place of arachis oil in the emulsions.

Animals↗
PubMed1979

C. parvum treatment of transplanted rat tumours of spontaneous origin.

C. parvum (Wellcome CN6134) has been examined for suppression of a range of transplanted rat tumours of spontaneous origin. With five tumours (three mammary carcinomas and two fibrosarcomas) growth of comparatively high cell inocula (with respect to the minimum for growth in control rats) was suppressed by admixture with the vaccine. Equivalent dry weights of Glaxo, Pasteur or Connaught BCGs were relatively ineffective. Intralesional injection of C. parvum into three three established tumours (two mammary carcinomas and one fibrosarcoma) retarded development of only one, the mmamary carcinoma Sp4. With three mammary carcinomas and one fibrosarcoma, active specific immune stimulation with vaccines of viable or irradiated cells admixed with C. parvum was again consistently effective only with carcinoma Sp4, and this tumour was also susceptible to intradermal but not intravenous treatment with C. parvum alone.

Animals↗