Andrew R. Thompsett

DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.

VH gene sequences from a novel tropical splenic lymphoma reveal a naive B cell as the cell of origin

The prevalence of malaria and other infections in tropical Africa provides a setting for the emergence of B‐cell tumours distinct from that in Western countries. Attempts to draw comparisons with Western lymphomas have led to difficulties, with so‐called African chronic lymphocytic leukaemia (CLL) having a different pattern of incidence from Western CLL. Splenomegaly is common in African CLL, and this has posed diagnostic problems in differentiating the tumour from malaria‐associated hyper‐reactive malarial splenomegaly (HMS). One feature of the splenomegalic form of African CLL is that the tumour cells often possess short but fine cytoplasmic projections reminiscent of those observed in Western splenic lymphoma with villous lymphocytes (SLVL). Analysis of Ig VH genes both facilitates discrimination between clonal B‐cell tumours and HMS, and reveals the differentiation status of the cell of origin. This study indicated that VH genes of nine cases of clonal splenic B‐cell tumours with villous lymphocytes from Ghana were relatively unmutated, consistent with an origin from a naive B cell. These features differ from SLVL which arises from a post‐follicular antigen‐selected B cell. One possibility is that these splenic B‐cell tumours derive from a splenic T‐independent B cell, with malaria infection as a potential influence.

DNA vaccination against cancer antigens

Rational approaches aimed at manipulating the immune system to act against cancer cells are now becoming feasible. There are two main reasons for this, both arising from developments in molecular genetics: first, there is a greater understanding of the tumor-associated changes occurring in cancer cells, some of which will generate candidate target antigens. Second, there is increasing knowledge of the processes involved in inducing an effective immune response. In attempting to activate the immune system against cancer, we need to remember that the major task of the immune response is to control or eliminate pathogens. Development of vaccines against cancer will rely on lessons from infectious diseases, and is bringing back together the fields of microbiology and immunology which had become separated, perhaps partly due to the effectiveness of antibiotics.

DNA fusion vaccines against B-cell tumors.

The ability of naked DNA to induce immune responses against encoded antigen has been clearly demonstrated for infectious diseases (1). In many cases, the induced immunity is able to protect against infection, and can approach the efficacy of exogenous antigen (2).