Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers.

Epidermal growth factor receptor (EGFR) is a cell surface molecule and member of the ErbB family of receptor tyrosine kinases. Its activation leads to proliferation, antiapoptosis, and metastatic spread, making inhibition of this pathway a compelling target. In recent years, an increasing number of clinical trials in the management of solid malignancies have become available indicating the clinical efficacy of anti-EGFR monoclonal antibodies and oral small molecule tyrosine kinase inhibitors (TKIs). This review addresses frequently used EGFR inhibitors, summarizes clinical efficacy data of these new therapeutic agents, and discusses their associated toxicity and management.

Embryonic vaccines against cancer: an early history.

Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

Induction of antitumor immunity through xenoplacental immunization.

Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

Immunoplacental therapy, a potential multi-epitope cancer vaccine.

The field of tumor immunology has made great advancements in recent years. A retrospective analysis of previous vaccine strategies combined with present knowledge may provide additional insight in this treatment modality. This article provides a review of immunoplacental therapy (IPT), a cancer vaccine consisting of chorionic villi extractions from the human placenta after a live full-term delivery. This therapy was first introduced in the 1970s by Valentin I. Govallo, M.D., Ph.D., who noted the immunological similarities between pregnancy and cancer. The goal of cancer immunotherapy, according to Govallo, is to view the fetal allograft as an "impregnating tumor" and create an immunological state in the oncological patient analogous to a spontaneous abortion in a pregnant women. The placenta shares identical growth mechanisms, antigenic determinants, and immune-escape properties with cancer cells; this includes numerous tumor-associated antigens, angiogenic growth factors, complement regulatory proteins, and defective apoptotic mechanisms which aid in their survival. Placental vaccination may function as a multi-epitope vaccine; the body recognizes the placental antigens of this vaccine as foreign, and thus stimulates a cross reactive humoral and cell-mediated immune response targeting cancer tumor-associated antigens as well as proteins that aid in cancer angiogenesis, complement regulation, and apoptotic resistance. With recent advancements in molecular and cellular cancer immunology, the model introduced by Govallo may provide an important strategic approach to cancer immunotherapy.