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Breakthroughs & Setbacks in Cancer Immunotherapies

Posted by Niveen M. Mulholland, Ph.D on Apr 13, 2016 11:00:00 AM

cancer_cells.jpgWhen President Nixon declared a war on cancer in 1971, scientists and the general public were energized about the possibility of eliminating these costly and deadly diseases. In the decades following, however, many initially promising treatments failed to deliver expected results. Although the medical community has become more skilled at targeting treatments to specific cancers, cancer remains the second most common cause of death in the United States.

Now, breakthroughs in immunological technology have renewed scientists’ enthusiasm and excitement about novel cancer treatments. Cancer immunotherapies have the potential to shift the medical landscape by reducing the toll the disease takes on patients and society at large.

 Renewed Excitement for Cancer Immunotherapy

Traditional treatments for cancer include surgical therapy, chemotherapy, and radiation treatment. These therapies are often used in combination to eliminate tumor cells and prevent their recurrence. Unfortunately, none of these therapies are specific to cancer cells. Surgical therapy often involves removal of healthy tissue adjacent to the tumor locus, as elimination of all cancerous cells is the top priority. Chemotherapy and radiation therapy are nonspecific treatments that destroy cancer cells as well as healthy cells. Combined, these therapies can have devastating effects on functional abilities and quality of life for cancer patients.

Recent positive clinical trials have renewed researchers’ interest in cancer immunotherapies. Immunotherapy provides a way to modulate a patient’s own immune system to mount a vigorous offensive against cancerous tissue. By using the body’s natural immune response against cancer cells, it is possible to avoid the collateral damage that results from traditional cancer therapies.

For example, researchers have found a way to reprogram T-cells -- the immune system’s killer cells that hunt down infected cells and cancer cells -- to act like antibody-based B cells. The result is an upregulation of immune system activity that hunts and destroys specific cells that have become cancerous, limiting the amount of collateral damage to healthy tissue.

Another cancer immunotherapy strategy that has piqued strong research interest is to modulate immune regulatory checkpoints. Immune checkpoint proteins are molecules that modulate the activity of the immune system. Cancer cells get around this system by inhibiting T-cell signals or other signalling molecules. Targeting inhibitory checkpoint molecules could remove the immune system’s inhibitory processes, helping it upregulate activity to fight against cancer cells.

Barriers and Challenges Remaining in the Fight Against Cancer

Despite the medical community’s renewed interest in and enthusiasm for cancer immunotherapy, several challenges remain. Researchers continue to seek ways to better modulate the immune system to improve sensitivity and specificity to attack cancerous cells without damaging adjacent tissue. Some of the major remaining challenges include:

  • Off-target toxicity for checkpoint inhibitors. By upregulating the immune response to cancer cells, checkpoint inhibitors remain an exciting target for cancer immunotherapies. However, there remain a spectrum of side effects that result from this immunologic enhancement. These may include endocrine, dermatologic, hepatic, and gastrointestinal events that develop because of increased inflammation or autoimmune activities.

  • Issues in large-scale production. New cell therapies must comply with the Food and Drug Administration’s Good Manufacturing Practices (GMP). This includes development of a closed manufacturing procedure that does not require open transfer between facilities. Furthermore, scientists must use clinical grade media and supplements to ensure the safety and reproducibility of the final product. Meeting these challenges is difficult for researchers with limited funding for stage I clinical trials.

  • Nonviral gene transfer. In animal research, viruses are used as vectors for gene transfer into tumor cells. However, use of viruses may compromise clinical safety and make large scale manufacture more challenging. In a recent breakthrough, researchers at the University of Texas MD Anderson Cancer Center found a novel approach to nonviral gene transfer known as the “Sleeping Beauty” system. This has been successfully employed to manufacture reprogrammed T-cells with specificity for tumor-associated antigens.

  • Decentralized manufacturing. Eventually, an end goal will be to create a manufacturing system whereby medical providers do not depend on a centralized manufacturing pipeline to create patient-specific cancer immunotherapies. It is desirable to process cells at the point-of-care for the most efficient, seamless delivery of resources to the patient. However, this creates significant procedural and regulatory hurdles that must be overcome.

Collectively, recent findings in the area of cancer immunotherapy have renewed researchers’ energy for the fight against cancer. Close partnerships between scientists, medical professionals, and biotechnology providers will be needed to overcome remaining hurdles and challenges.

Do you work with immunotherapies?  If so, please share some of your challenges and success stories in the comments below.

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