Early experience with novel immunomodulators for cancer treatment

Abstract

Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. It is now known that this relationship is quite complex and only some of the interactions have been elucidated. Early attempts at immunotherapy, such as Coley's toxins, were undertaken without an understanding of the processes mediating the effects. With a better understanding of the immunology of this anticancer response, recent trials have focussed on certain aspects of the process to stimulate an antitumour response. In this review, the authors discuss a number of novel biological response modifiers that work as general stimulants of the immune system, through varied mechanisms including induction of stimulatory cytokines (such as IFN-alpha, TNF-alpha and IL-12) and activation of T cells and the antigen-presenting dendritic cells. These compounds include Toll-like receptor agonists, several of which are in clinical trials at present. In addition to immunomodulatory activity, some compounds such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide and its analogues also target existing or developing tumour vasculature. Some of these compounds have single-agent activity in clinical trials, while others such as DMXAA have shown promise in combination with chemotherapy without increasing toxicity. Lactoferrin is another compound that has shown clinical activity with low toxicity. At present, accepted indications for immunotherapy are limited to a few cancers such as renal cell carcinoma and melanoma. This paper looks at some of the reasons for the limited impact of immunotherapy so far and suggest possible avenues for further research with a greater likelihood of success.

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

“…Approved by the FDA in 2004, imiquimod is used as a topical ointment for the treatment of primary superficial basal cell carcinoma (BCC) [95]. This compound binds to the endosomal TLR7 of plasmacytoid DCs (pDCs), leading to the production of proinflammatory cytokines like IFN-α, TNF-α, IL-12, among others [94,95].…”

“…This compound binds to the endosomal TLR7 of plasmacytoid DCs (pDCs), leading to the production of proinflammatory cytokines like IFN-α, TNF-α, IL-12, among others [94,95]. As a result, skin macrophages and other innate immune cells become activated, releasing reactive oxygen species (ROS) and toxic byproducts [95]. It is thought that high concentrations of imiquimod can lead to the specific apoptosis of tumor cells in the skin [94,95].…”

“…As a result, skin macrophages and other innate immune cells become activated, releasing reactive oxygen species (ROS) and toxic byproducts [95]. It is thought that high concentrations of imiquimod can lead to the specific apoptosis of tumor cells in the skin [94,95].…”

Protein Kinases and Protein Phosphatases as Participants in Signal Transduction of Erythrocytes

“…Lactoferrin (Lf) is a metal-binding glycoprotein with antioxidative , antiinflammatory, immunomodulatory (Legrand et al, 2004), anticancerogenic (Thotathil and Jameson, 2007) anti-bacterial (Weinberg, 2007), antiviral (Mistry et al, 2007), antiatherogenic (Kajikawa et al 1994), and antithrombotic properties (Levy-Toledano et al, 1995).…”

Spontaneous Regression of Clear Cell Carcinoma of the Endometrium

“…On cellular level the induction of spontaneous regression is completed by either cell differentiation or cell death [5]. In some cases tumour regression was preceded by surgical procedures [6]- [8]; the role of infectious agents and febrile reaction [9]- [13] as well as changes in metabolic processes (especially glucose metabolism) [14] [15] in the regression of cancer is also well documented.…”