Emerging Targets in Cancer Immunotherapy

Professor Lana E. Kandalaft, PharmD, PhD, MTR, is the director of the Center of Experimental Therapeutics at CHUV/UNIL in Lausanne, assistant professor at the Ludwig Institute for Cancer Research (Lausanne Branch) and department of oncology, CHUV/UNIL, and adjunct assistant professor at the Ovarian Cancer Research Center, University of Pennsylvania, school of medicine.

Professor Kandalaft is an expert in translational cell based cancer immunotherapies with a special focus on immunotherapy of ovarian cancer. Cancer Network spoke with Professor Kandalaft about emerging dendritic cell targets, treatment cost, and the future of cancer immunotherapy.

Cancer Network: What will the next generation of cancer immunotherapy look like? Are decades of research into cancer vaccines about to culminate to yield a new generation of treatment options?

Dr. Kandalaft: Although the current immune checkpoint blockade therapies and engineering T cells have shown effectiveness in many types of cancers and even complete tumor elimination in some cases, the high cost of these therapies make them inaccessible for a large number of patients in the United States and worldwide-especially in the third-world countries. They also are indicated for only a certain population of cancer patients.

We need to develop new cancer therapies that can be manufactured very quickly and at a low cost, and at the same time can be given to a wide variety of patients in all disease stages. We believe that the next generation of cancer immunotherapy will comprise the administration of synthetic agents called toll-like receptor (TLR) agonists to activate beneficial anti-tumor responses in patients. Some TLR agonists, such as PolyI:C, MPLA [monophosphoryl lipid A] and Imiquimod have already been approved by FDA and used for cancer treatments, and have shown effectiveness.

Novel TLR agonists are also being developed and tested in clinical trials. The use of TLR agonists may circumvent the need to use expensive immunotherapies. These can be used in combination with standard of care therapy such as cryoablation, radiation, or immunogenic chemotherapy.

Cancer Network: What role do dendritic cells play in innate and adaptive immune system activation?

Dr. Kandalaft: Dendritic cells are the master regulators of the human immune responses, including activating responses that control tumors. Their main role is survey the tumor microenvironment and present the foreign tumor-derived proteins and peptides to the T cells. T cells will respond and become activated against the tumors and eliminating them.

Cancer Network:  Which targets of dendritic cells show the most promise in cancer vaccination? Are there promising multi-target dendritic cell vaccination strategies in development?

Dr. Kandalaft: Our recently published study in ovarian cancer patients showed that the dendritic cell vaccines made out of patients’ own tumors could elicit T cell responses against tumor neoantigens. This class of antigens are highly specific to the patients as they are based on the mutations present in individual patients. Thus, we believe that personalized dendritic cell vaccines pulses with patients’ own tumors or with peptides made against neoantigens specific for the patients can be used to prime and expand T cells recognizing neoantigens for durable tumor control.

Cancer Network: Do you foresee dendritic cell-targeting cancer vaccines supplanting or supplementing immune checkpoint inhibition immunotherapy?

Dr. Kandalaft: We believe that they could be supplementing immune checkpoint inhibition immunotherapy. Our group and others have shown that dendritic cell-targeting vaccines are effective in different cancer types. However, only a small number of patients remain tumor-free after dendritic cell treatment. We believe that dendritic cell vaccines and immune checkpoint inhibition immunotherapy are highly complementary for cancer treatment.

Cancer Network: What are particularly promising, currently-active clinical trials that are testing dendritic cell-target vaccination strategies?

Dr. Kandalaft: We found a number of recent clinical trials using dendritic cells to target cancer stem cells that are interesting. A number of studies have shown that tumor growth and recurrence of many cancers appeared to be driven by a population of cancer stem cells. We also believe that dendritic cells could be genetically modified to make them more potent in activating T cells, for example introducing genes that secret proteins that activate T cells is a promising avenue to purse.