Animal Models for Tumor Localization
Many factors influence the uptake of radiolabeled monoclonal antibodies (mAbs) in tumors. Some are dependent on the antibody, such as affinity, intact immunoglobulin or fragment, route of administration, choice of radio isotope, or method of labeling. Oth
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13 Animal Models for Tumor Localization Gail Rowlinson-Busza 1. Introduction Many factors influence the uptake of radiolabeled monoclonal antibodies (mAbs) in tumors. Some are dependent on the antibody, such as affinity, intact immunoglobulin or fragment, route of administration, choice of radio isotope, or method of labeling. Others depend on properties of the tumor, such as site, size, vasculature, and antigen density on the tumor cell surface. Animal models for studying these parameters are usually based on mice or rats bearing transplanted tumors. In this chapter, various tumor model systems will be described with some discussion of what data can be obtained using them. 2. Immunodeficient Animals 2.1. History The idea of transplanting tumors into foreign hosts is not new, but it was not until the beginning of this century that it was realized that this was most successful if the donor animal was related to the recipient (1). This led to a proposed theory of inheritable susceptibility to tumor transplantation (2), but the nature of the process was unknown. It was initially supposed that antibodies against the tumors were responsible for their rejection. A major advance was the advent of inbred strains of mice, in which many generations of sibling matings produced animals that were all homozygous for the same genes. This allowed the allotransplantation of tumors and other tissues from one animal to another in these genetically homogeneous mice, and also to F1 hybrids of the pure line and another strain. This led Haldane (3) to propose that there were antigenic variations on all tissues, similar to blood group antigens. Medawar (4) demonstrated, in experiments on skin-grafting in rabbits, that a second From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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allograft to the same recipient from the same donor was rejected more quickly than the first. In 1961, Miller (5) elucidated the immunological function of the thymus. He demonstrated that neonatally thymectomized mice tolerated skin grafts from a different mouse strain for up to 2 mo, but that intact mice and thymectomized mice, which were then grafted with thymuses, rejected the grafts within 2 wk. Warner et al. (6) reported similar findings in bursectomized chickens. Therefore, if human tumors were to be transplanted successfully in experimental animals, some method of overcoming immunological rejection had to be found.
2.2. Immunologically Privileged Sites Initially, immunologically privileged sites were found to be capable of sustaining tumor xenograft growth. Murphy (7) was able to grow rat sarcomas in the outer membrane of chick embryos. Successful transplants of some human tumors in the anterior chamber of the eye in rabbits and guinea pigs was reported by Greene (8) but most tumors regressed or did not grow at all. In a review of his attempts between 1939 and 1950 to transplant tumors into the anterior chamber of the e
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