Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI.

The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.

Cancer immunology: highlights of the NCI Extramural Immunology Program.

The long-term goal of research supported by the Immunology Program is to better understand immune mechanisms and their regulation in order to develop more effective strategies to strengthen the immune response against cancer. While there has been much progress in the field of immunology in recent years, many major questions remain unanswered. The role of MHC antigens in regulating the immune response to tumors is still unclear, as is the nature of putative tumor-associated antigens which are the targets of this response.

Kinetics of immunoglobulin and specific antibody responses of CBA mice infected with Trypanosoma rhodesiense.

Groups of CBA/CaJ and B-cell deficient CBA/N mice were infected with Trypanosoma rhodesiense EATRO 1886 strain. Survival, parasitaemia, serum Ig levels plus specific trypanosomal IgM and IgG antibodies were assayed and compared during infection. Whereas both strains of mice had similar parasitaemias during the first week of infection, CBA/N parasitaemias were lower than those observed in CBA/CaJ mice during the subsequent study period.

Induction of T cell activity in athymic (nu/nu) mice infected with Trypanosoma rhodesiense.

Infection of C57BL/10 (B10)3 nu/nu mice with Trypanosoma rhodesiense results in the development of significant T-cell reactivity in spleen and lymph nodes. The proliferative responses to mitogens, such as concanavalin A (Con A) and phytohemagglutinin (PHA), and in mixed-lymphocyte reactions (MLR) to alloantigens are enhanced compared with control uninfected nu/nu mice. These results serve to emphasize the stimulatory nature of trypanosomes on the immune system.

Iodination and identification of surface membrane antigens in procyclic Trypanosoma rhodesiense.

Surface membrane proteins and glycoproteins of procyclic Trypanosoma rhodesiense were labeled with 125I by the use of the insoluble catalyst Iodo-Gen. Autoradiography of whole solubilized procyclic trypanosomes after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed a minimum of 25 surface components to have incorporated radioactivity. These components ranged in m.

Survival of mice injected with Plasmodium vinckei or Plasmodium yoelii XL by the footpad route.

NIH-white mice were injected with varying doses of Plasmodium vinckei or Plasmodium yoelii lethal via the hind footpad (FP), intraperitoneal (IP), subcutaneous (SC) routes. Survival was dependent on the dose of the inoculum and route of injection. Injection via the IP and SC routes led to higher mortality than the FP route.

Non-specific immune responses in CBA/N mice infected with Trypanosoma brucei.

CBA/N mice carry a genetic defect which causes a maturational arrest of normal B lymphocyte development, and results in an inability to mount IgM antibody responses against certain T lymphocyte-independent antigens. These mice were found to survive an experimental infection with Trypanosoma brucei two to three times longer than conventional mice. This enhanced survival does not appear to be related to the level of infection of the host since parasitaemias were similar in all strains tested.

Vole population cycles: A case for kin-selection?

Kin-selection, as evidenced by aggression between individuals with a low coefficient of relation, may be a significant contributing factor in vole population cycles. Demographic and behavioral studies support this idea.

Delayed-type hypersensitivity in mice immunized with Trypanosoma rhodesiense antigens.

When mice were immunized intravenously, subcutaneously, or by the footpad route with formaldehyde-killed Trypanosoma rhodesiense, delayed-type hypersensitivity was elicited by the use of frozen-thawed trypanosomal antigen. The delayed footpad swelling technique was used to measure delayed hypersensitivity. Hypersensitivity induction was dose dependent (greater than or equal to 10(6) formaldehyde-treated T.

The induction of immunologic tolerance with type III pneumococcal polysaccharide cross-linked or coupled to protein.

Type III pneumococcal polysaccharide molecules were linked to one another, i. e. cross-linked.

Prevention of recrudescent malaria in nude mice by thymic grafting or by treatment with hyperimmune serum.

Nude mice died when infected with the normally avirulent malarial parasite Plasmodium berghei yoelii. Furthermore, malaria recrudesced in Nu/Nu mice after the termination of acute disease by treatment with clindamycin. Recrudescence was not observed in Nu/Nu mice that had been grafted with thymic tissue or treated with hyperimmune serum.

Delayed immune reactions in mice immunized with malarial antigen.

Mice were immunized subcutaneously, intravenously or in a footpad with antigens prepared from a lethal strain of Plasmodium berghei yoelii. A delayed footpad swelling (DFS) reaction was observed 4 days after immunization, and was detectable at least 42 days after immunization. However, IV immunization was the least efficacious is producing hypersensitivity.

Cyclophosphamide pretreatment and protection against malaria.

Mice pretreated with cyclophosphamide were able to overcome infection from a lethal malarial strain. The development of resistance was preceded by increased hypersensitivity to malarial antigens. Hypersensitivity was demonstrable by a delayed footpad swelling technique.

Cross reactivity between Anaplasma marginale and two Plasmodium species as demonstrated by passive hemagglutination.

Two types of antigens were prepared from each of 3 partially purified preparations of Anaplasma marginale, Plasmodium lophurae, and P berghei. Hemagglutination tests were conducted with homologous serums to detect antigenic relationships between these organisms. Serums were also absorbed with both homologous and heterologous antigen preparations.