Jean Jones

Tumour localization of monoclonal antibody against a rat mammary carcinoma and suppression of tumour growth with adriamycin-antibody conjugates

SummaryMonoclonal antibody to the rat mammary carcinoma Sp4 isolated from hybridoma supernatants and labelled with 125I showed preferential in vivo localization into subcutaneous growths of Sp4 compared with normal tissues and a range of other transplanted tumours. No specific localization was seen with 125I-labelled normal rat immunoglobulin. Adriamycin conjugated to monoclonal antibody significantly retarded Sp4 tumour growth at 1/25th of the effective dose of the free drug, and in some cases brought about total tumour regression. Normal rat immunoglobulin-adriamycin conjugates were relatively ineffective. These studies indicate that monoclonal antibody directed against tumour cell surface antigens may be highly effective for tumour targeting of therapeutic agents.

Ambulatory esophageal pH monitoring in children as an indicator for surgery

Twenty-four-hour esophageal pH monitoring was performed in 59 children with symptoms of gastroesophageal reflux using a miniature pH electrode and a portable recording system to establish the diagnosis. Significant reflux was seen in 26 (44%) of the patients and these were treated for six weeks with cimetidine, Gaviscon, and Nestargel. Five children who did not improve either symptomatically or on repeat pH monitoring while on treatment underwent antireflux surgery. The pretreatment reflux index in this group was 26.5 compared with a pretreatment reflux index of 11.2 in the 21 patients who improved on therapy (P less than 0.01). Esophageal pH monitoring has enabled selection of children for surgery and may be used as an early indicator of those who will not benefit from long-term medical therapy. Ambulatory and home monitoring techniques are more convenient and cost-effective and allow studies to be performed in the normal home environment.

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.

Monoclonal Antibodies to a Tumor Specific Antigen on Rat Mammary Carcinoma Sp4 and Their Use in Drug Delivery Systems

With the development of techniques for producing monoclonal antibodies to cell surface antigens, the identification and typing of tumor-associated antigens is entering a new and sophisticated phase (Baldwin et al, 1981). There are, for example, a range of monoclonal antibodies which react with antigens associated exclusively, or more frequently at greatly increased levels, on human tumors including malignant melanoma, osteogenic sarcoma, neuroblastoma and colon carcinoma (see chapters 9–11, this volume). These monoclonal antibodies may have several applications in addition to their use for isolating and identifying tumor-associated antigens. This includes the use of radioisotopically labelled antibodies for identification of tumor deposits by Y-scintigraphy. Additionally monoclonal antibodies may be used as carriers for anti-tumor agents, thus providing an approach for selective attack upon malignant cells. There are several options available in the choice of anti-tumor agents but currently, attention is being given to plant and bacterial toxins, cytotoxic drugs and biological response modifiers including interferon (Baldwin et al, 1981: Baldwin and Byers, 1982).