Jean Gaillard

Immunological castration by a totally synthetic vaccine: modification of biological properties of LH-RH after conjugation to adjuvant-active muramyl peptide.

Recently, we demonstrated that immunological castration of male mice can be obtained by immunization with Luteinizing Hormone-Releasing Hormone (LH-RH) directly coupled to NAcMur-L-Ala-D-isoGln-L-Lys (MDP-Lys) without carrier and Freunds Complete Adjuvant (FCA) but in the presence of Polyvinyl-Pyrrolidone (PVP). In the present report, we have observed that: (a) immunization by the conjugate, LH-RH-MDP-Lys, was very effective even in absence of PVP, and this conjugate was more active than other conjugates containing MDP coupled to LH-RH fragments; (b) a strong secondary response could be observed by the administration of free LH-RH suggesting that the endogenous secretion of LH-RH might elicit a boosting effect; (c) administration of MDP-Lys coupled to LH-RH decreased the pyrogenicity of the glycopeptide; (d) such a conjugation also decreased the hormonal activity of the antigen although it enhanced its immunogenicity. These results show that a conjugate (2000 dalton) of a decapeptide hormone with a synthetic adjuvant glycopeptide can induce immunological castration in mice after administration in saline. The immunopharmacological properties of the conjugate and its conditions of efficacy suggest that such an approach could find clinical application.

Structural requirements for the induction of immunological castration by linear monomeric LHRH-LYS-MDP administered in saline

It was previously shown that castration could be obtained in male mice by immunizing them in saline with a conjugate referred to as LHRH-Lys-MDP and containing the decapeptide hypothalamic hormone LHRH covalently linked to the adjuvant glycopeptide MDP-Lys. Since coupling was made using carbodiimide, it could have produced oligomers or isomers as well as monomers. In the present investigation male and female mice were immunized in saline with a linear monomeric MDP linked LHRH molecule obtained by total synthesis. Histological studies showed gonadal alterations in both male and female mice. The study of analogs provided a correlation between the castrative activity of LHRH-Lys-MDP and its chemical and antigenic structures. However, because LHRH antibody levels were not very high, mechanisms other than antibody response are discussed. Such totally synthesized molecules including a safe adjuvant could make a clinical use of LHRH immunization possible in endocrine-dependent cancers.

Immunocytochemical Quantitative Study of Alpha-Fetoprotein in Normal and Neoplastic Neural Development

The presence of alpha-fetoprotein (AFP) was studied in developing nervous tissues: rat cerebral cortex and neuroepithelial derivatives of a murine teratocarcinoma. AFP was localized by an indirect immunohistoperoxidase technique. Using serial dilutions of anti-AFP antibodies, the end-points of staining (minimal concentration of antibodies giving a positive labelling) were established. These points enabled the evaluation of the amount of stained AFP at different periods of development. In rat cerebral cortex, AFP showed one maximum amount on the 19th-20th day postcoitum (in moderately differentiated structures), and two minima on the 13th-14th day (in primitively differentiated ones) and the 28th-29th day (in well-differentiated ones), respectively. Similarly, one maximum and two minima were established in the derivatives of teratocarcinoma imitating normal neural development.

Localization immunohistochimique de la gonadothrophine chorionique et de l'alpha-foetoprotéine dans les polyembryomes: Description et interprétation

Summary As polyembryomas are special forms of human teratomas in which numerous structures mimicking the early stages of the human embryo are conspicuous, immunoperoxidase staining of these embryoid bodies (EB) has been used to reveal the initial appearance and localization of βHCG and AFP, respectively, in amnion and in primary yolk-sac. EB are involved in the building of various questionable patterns of teratomatous germ-cell tumours. Special emphasis has been placed on tracking yolk-sac tumour patterns through dislocating EB, using a specific anti-human AFP serum.

Une technique immunologique (immunoperoxydase ABC) permet de déceler une différenciation hépatique dans les tératocarcinomes de la souris

Summary The present work shows that hepatic tissue occasionally appears in certain mouse teratocarcinomas: the presence of hepatic structures in these tumours, suspected on the basis of routine histological examination, is confirmed here by the use of anti-mouse alpha-fœtoprotein serum and the ABC immunoperoxidase technique.

Le marquage immunologiquede l'α-ftoprotéine dans l'endoderme proximal et sa signification dans les différenciations extra-embryonnaires des tératocarcinomes de la souris

Summary The ABC technique using a specific anti-mouse α-fœtoprotein (AFP)serum permits identification of groups of extraembryonic proximal endoderm cells in certain teratocarcinomas. These AFP + cells are always associated with trophoblastic and parietal endodermal patterns and structures. These observations strongly support the hypothesis of a common precursor to the extraembryonic tissues which appears during the first phases of egg development.

FACTORS ACTING UPON DIFFERENTIATION OF MOUSE TERATOMA IN VIVO: SPONTANEOUS DIFFERENTIATION AND EFFECTS OF INTERFERON

CE/44 mouse teratocarcinoma and its sublines isolated at the Institut Pasteur were studied comparatively in 129/Sv, hybrid F1 129 X NCS, and NCS strains of male and female mice with respect to the age of the animals and the type of the tumor graft (ascitic or subcutaneous solid tumor). The tumors grow more quickly and with more malignant characteristics in female mice. The tumor takes and growth are equally good in the hybrid F1 as in 129/Sv mice, but its maintenance in hybrid F1 is not so stable, for a tumor loss and a lessening of differentiation could be seen through the passages in this strain. In the NCS strain the tumor grows very rarely. Interferon slowed the subcutaneous tumor growth and favored neuroepithelial tissue differentiation, but allowed selective growth of one cellular type, the trophoblastic one, which is very malignant, and which, in the ascitic tumor, caused death in female animals by a hemorrhagic syndrome.