Cancer Immunotherapy:

A: Dendritic cell therapy

Dendritic cells are the most potent antigen presenting cells that are capable of activating the immune system against cancer cells. The dendritic cells cancer vaccine based immunotherapeutic approach has emerged as one of alternative treatment options owing to its low toxicity in comparison to other standard methods. The clinical efficacy has been demonstrated with improvement in overall survival rate and low toxicity.

The application of ex vivo generated DCs emerged in an effort to improve the therapeutic efficacy in cancer patients with dysfunctional endogenous DCs. The most commonly used approach is the differentiation of DCs from peripheral blood mononuclear cells (PBMCs) obtained from peripheral whole blood or leukapheresis procedures. These DCs are called monocyte-derived DCs (moDCs). CD14+ monocytes are first selected from PBMCs either by plastic adherence or positive selection using immunomagnetic beads. The monocytes are induced to differentiate into immature CD14-, CD83- DCs by culturing for several days in the presence of Interleukin-4 (IL-4) and granulocyte macrophage colony stimulating factor (GM-CSF).

The immature DCs are activated to become mature by culturing for an additional 1-2 days in the presence of a maturation stimulus. Mature DCs are characterized by presence of CD80 and CD86, CD40, CD70, or inducible T-cell co stimulator ligand (ICOS-L) molecules.

In the last decade, a large number of clinical trials were carried out to establish the therapeutic efficacy of DC vaccines. Among the over 200 DC based clinical trials, most of the cancer patients treated and established the feasibility and safety of DC vaccines.

At NOVO, we exploit the potential of DC vaccine to improve the lives of patients. Importance is given in improving the efficacy of the DC vaccines and applying new strategies for delivering effective, durable and anti tumor immune response in solid multiple maligencies.

B: Adoptive Tumor Infiltrating Lymphocytes (TILs) Therapy

Immunotherapy using adoptive T cells has emerged as one of the potent treatment options for metastatic tumors. TILs are activated and expanded under ex vivo conditions so that they respond to tumor cells specifically. The existence of lymphocytes in tumors is often associated with better clinical outcomes and reflects tumor-host interaction. The TILs therapy has demonstrated high overall response rates, resulting in tumor regression and prolonged survival in comparison to IL-2 and ipilimumab treatments. Expansion of TILs under ex-vivo conditions using patients’ own tumor tissue is a prerequisite for effective adoptive transfer immunotherapy. The process involves growing cells in the presence of IL-2 and further expansion with tumor reactive cells.

C: Combination approach:

It is evident that the field of adoptive cellular therapy is growing fast. Several types of immunotherapy have shown great clinical impact. Cellular cancer therapies like dendritic cell therapy, activated T cell therapy and TILs are becoming more popular choices of cancer treatment due to the generation of clinically effective antitumor response and relatively low side effects. Treatment with combination of DC and TILs in patients with early stage cancer may provide us more insights in this field. Cancer immunotherapy needs further in-depth investigations on combination approaches that can improve long term efficacies and reduce the cost to a more affordable level.
Reference: Bora CR et al 2015. Trends in Adoptive Tumor Infiltrating Lymphocytes (TILs) Therapy. BAOJ Cancer Res Ther 2: 006.