G. Dranoff – Cancer Immunology and Immunotherapy

Автор: G. Dranoff
Название книги: Cancer Immunology and Immunotherapy
Формат: PDF
Жанр: Медицина
Страницы: 319
Качество: Изначально компьютерное, E-book

Cancer Immunotherapy discusses tumor-immune interactions in several human cancers. The text proposes an integrated scheme of the impact of local immune reactions on clinical outcome, and illustrates various aspects of this complexity.

The recent FDA approval of Provenge1 as the first therapeutic cancer vaccine
together with the recent demonstration that Ipilimumab1, a monoclonal antibody
that blocks a negative immune checkpoint called cytotoxic T lymphocyteassociated
antigen-4 (CTLA-4), prolongs patient survival are major achievements
that usher in a new era of cancer immunotherapy (Hodi et al. 2010; Kantoff et al.
2010). These “first-into-class” treatments reflect the substantive progress that basic
and translational scientists have made toward understanding the mechanisms underlying
protective tumor immunity in cancer patients.
Immunotherapies were first explored at the turn of the twentieth century, but the
crafting of potent treatments required more detailed knowledge of how the immune
system responds to cancer. Advances in genetic, cellular, and biochemical technologies
have begun to yield this critical information, which has stimulated the
development and widespread application of monoclonal antibodies and bone marrow
transplantation as highly beneficial therapies for many solid and hematologic
malignancies. Moreover, recognition of the pathogenic involvement of microbial
agents in cancer resulted in the generation of effective preventive vaccines against
hepatitis B virus and human papilloma virus, which have and will significantly
reduce the incidence of liver and cervical cancer, respectively.
The success of Provenge1, Ipilimumab1, and likely other cancer immunotherapies
in the near future derives from a richer characterization of the processes of
immune recognition and immune regulation. Dendritic cells are specialized to
present cancer antigens to effector lymphocytes through a pathway that involves
both positive and negative signals. In turn, the activities of effector lymphocytes are
modified in the tumor microenvironment through mechanisms that normally contribute
to the maintenance of self-tolerance. Moreover, in the context of an ineffectual
host response, tumors evolve to exploit factors present in the microenvironment
that facilitate disease progression. Thus, therapeutic manipulation of immune
recognition, immune regulation, and tumor-promoting inflammation should prove
decisive in triggering immune-mediated tumor destruction. This volume brings together 13 groups that have made major contributions to
the study of endogenous and therapeutic tumor immunity in model systems and
patients. Collectively, these investigations have generated remarkable insights into
the complex cross-talk between the tumor and host. This knowledge should render
possible the identification of specific molecular mechanisms that restrain protective
immunity in individual patients; this information will thereby guide the administration
of appropriate immunotherapeutics to overcome these limitations and markedly
impact patient outcome. It is likely that a combination of immune approaches
that address complementary defects will prove most potent, and that immune
treatments will be effectively integrated with other strategies for cancer therapy