Dendritic cell cancer immunotherapy

The basic idea of cancer immunotherapy is to get a patient’s own immune system to attack and destroy cancer cells or cancer stem cells or both. There are several approaches to doing this and one important general approach involves the use of dendritic cells (DCs).  Dendritic cells are immune system cells that help determine the adaptive immune response.   In simple language dendritic cells identify pathogens and then go tell the T cells what those pathogens are so the T cells can go out and kill cells harboring those pathogens.   “Immature dendritic cells constantly sample the surrounding environment for pathogens such as viruses and bacteria. This is done through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs). — Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and begin to migrate to the lymph node.”  There, “they act as antigen-presenting cells: they activate helper T-cells and killer T-cells as well as B-cells by presenting them with antigens derived from the pathogen, alongside non-antigen specific costimulatory signals(ref).” Finally, the helper and killer T-cells go out and kill any cells presenting the antigens. 

So, the general strategy in dendritic cell cancer immunotherapy (DCCI) is to make sure a significant subpopulation of dendritic cells are primed with antigens unique to cancer stem cells or cancer cells of the kind concerned.  There are various ways to make this happen.  In the case of skin cancers one approach is to paint the surface of the cancer with an “eat me” substance that will be recognized by already-circulating dendritic cells(ref). “In mice, topical application of phosphatidylserine-containing ointment over melanoma induced tumor-specific CTL, local and systemic antitumor immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy(ref).”  A second DCCI approach is to collect a sample of a patient’s dendritic cells (normally from bone marrow), label these cells with the cancer antigen, and then inject them back into the patient(ref).  A third and new DCCI approach reported only yesterday is to start with embryonic stem cells, engineer these so they become dendritic cells, label these cells with the cancer antigen and inject them into the patient. According to a press release: “Geron Corporation (Nasdaq: GERN) today announced the publication of data demonstrating that dendritic cells (DCs) scalably manufactured from human embryonic stem cells (hESCs) exhibit the normal functions of naturally occurring human DCs found in the bloodstream. These findings support the use of hESC-derived DCs in therapeutic vaccine applications for cancer and other diseases. Substituting standardized, off-the-shelf hESC-derived DCs for current approaches using DCs obtained from individual patients may result in more cost effective and reliable approaches to cancer immunotherapy(ref).“

Research related to DCCI  has been going on for over 10 years now and despite several problems that have been encountered shows potential promise against several cancer types.  These articles review progress and problems in developing an effective dendritic cell vaccine against melanoma(ref)(ref). A recent publication suggests a variant of DCCI where dendritic cells are pulsed with RNA(ref).  A 1999 publication suggested the application of DCCI to two incurable diseases: Dendritic cell immunotherapy for cancer: Application to low-grade lymphoma and multiple myeloma.  A 2008 report indicates “The clinical studies have shown that DC administration to patients is safe and induces antigen-specific immunity. However, it seldom elicits objective clinical responses in patients with advanced-stage malignancies. Novel insights into DC and lymphocyte regulation are expected to lead to more effective vaccines in the near future(ref).”  In other words, the desired therapeutic effectiveness is mostly not there yet for people with advanced cancers but there is hope that more effective DCCIs can be developed.

I need point out again that there are other approaches to cancer immunotherapy besides use of dendritic cells, for example ones based on using monoclonal antibodies.  These too are potentially promising and in some cases have been shown to be successful.  But these will have to be topics of another blog post.