On August 22, CRISPR Therapeutics and Massachusetts General Hospital Cancer Center (MGHCC) announced a two-year research collaboration to develop T-cell cancer therapies. The CRISPR-Cas9 gene editing technology will be used to improve upon existing cancer cell therapies and focus on the specific needs of patients with blood cancers and tumors.
In the past few years, immunotherapy has gained traction in treating cancer patients—specifically, adoptive cell therapy (ACT). ACT uses a patient’s own immune cells to fight malignant cancer cells. One type of ACT, called CAR T-cell therapy, is close to being approved by the FDA. CAR T-cell therapy has been very successful at treating patients with advanced blood cancers in small clinical trials and has recently been approved to treat children with acute lymphoblastic leukemia.
Bringing CRISPR-Cas9 into the mix could make it easier for researchers and doctors to genetically engineer patient cells to attack malignant cells. Targeted drug therapies like imatinib and trastuzumab are being used to target cancer cells based on molecular charge—using CRISPR, patient cells could be modified to do this on their own.
In March 2017, researchers reported the successful use of CAR T-cell therapy in mice using CRISPR. In the study, immune cells engineered with CRISPR were more effective at killing tumor cells than conventionally-engineered immune cells. The CRISPR-engineered cells were also more effective for a longer period of time than traditionally engineered cells and were less likely to stop recognizing and attacking malignant cells after a certain length of time.
Before the popularization of CRISPR, an extremely precise gene editing tool, retroviruses were used to deliver the required genes to patients. As a result, the genes were deposited in random locations in the patient’s genome. This left open the possibility of unintended genetic consequences, as researchers could not control where the new gene was inserted. With CRISPR, researchers can control where in a patient’s genome the new gene is deposited, leading to a lesser likelihood of unintended consequences.
Currently, immunotherapy works by extracting immune cells from a patient’s blood. The cells are then genetically modified in a lab, reproduced, and then returned to the patient’s body to, hopefully, eliminate cancer cells. However, one new trial in China will attempt to edit immune cells via CRISPR without removing them from the patient’s body. The goal of this particular trial is to prevent and eliminate cervical cancers caused by the human papilloma virus (HPV).
CRISPR has already been used to treat patients with HIV by disabling a receptor gene the virus uses to enter a patient’s cells. Doctors removed HIV patients’ immune cells—like with cancer immunotherapy patients—disabled the receptor, and returned the resistant cells to the patient’s body to multiply.
Researchers at the University of Rochester have found yet another use for CRISPR in slowing and stopping the growth of tumors. When a cell becomes cancerous, it grows and divides continually, invading the surrounding tissue and killing healthy cells. In the study, scientists targeted the Tudor-SN protein, which prepares cells for division. Once the Tudor-SN protein was removed, the genes encouraging cell growth were slowed. By interrupting the propagation of cancerous cells, researchers hope to stop the growth of tumors.
For now, CRISPR-Cas9 cancer treatments are primarily limited to clinical trials. Though human trials have been successful in other fields, it may take several years before gene editing is widely used to treat patients with cancer.
Top 10 Cancer Centers by Net Patient Revenue
|Hospital Name||Net Patient Revenue||# Staffed Beds|
|University of Texas MC Anderson Cancer Center||$2,992||660|
|Memorial Sloan Kettering Cancer Center||$2,531||476|
|James Cancer Center Hospital & Solove Research Institute||$1,197||306|
|Dana-Farber Cancer Institute||$884||30|
|Moffit Cancer Center||$779||206|
|Sylvester Comprehensive Cancer Center||$637||40|
|Seattle Cancer Center Alliance||$494||20|
|Roswell Park Cancer Institute||$459||133|
|Hospital of the Fox Chase Cancer Center||$317||100|
|Karmanos Cancer Center||$234||122|
Fig 1 Data from Definitive Healthcare
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