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Although CAR-T cell therapy offers many cancer patients a chance of recovery, the technology has some significant drawbacks. Treatment is complex and ExpensiveIt is time-consuming and often difficult to access, requires invasive procedures, There is a significant risk.
In vivo CAR T cell therapy has the potential to be a game-changer in a global market that is expected to reach 1 million people in the future. $88.5 billion by 2032This investigational technology avoids external manufacturing and instead uses gene vectors to modify immune cells within the body, eliminating many of the drawbacks of both autologous CAR-T and experimental off-the-shelf allogeneic treatments, potentially making cell therapy accessible to more patients and applicable to new indications, including autoimmune diseases. Big promises.
“If in vivo CAR-T is successful and maintains all the benefits, such as the robust efficacy of biological drugs, while eliminating all of the limitations, then autologous CAR-T and even allogeneic CAR-T can and should become obsolete,” said Dr. Ramin Farzaneh Far, chief medical officer at Capstan Therapeutics. “That’s really our vision: to maintain all the benefits and eliminate all the drawbacks.”
“If any of us could show that this works, it would dramatically change the field.”
David Fontana
Chief Operating Officer, Umoja Biopharma
The field is moving forward rapidly, with four companies rumored to be filing INDs this year or next, according to David Fontana, chief operating officer at Umoja Biopharma, an early-stage CAR T-cell therapy company.
“I’d like to believe we’re the first,” Fontana said. “I’m confident we’ll be able to get into the clinic this year.”
Rethinking your approach
The FDA has approved six autologous CAR-T cell therapies for blood cancers since 2017. Treatment requires a multi-step process in which T cells are harvested from the patient, reprogrammed to find and destroy cancer cells, expanded, and reinfused.
Slow manufacturing processes and capacity bottlenecks lead to some patients dying. Before treatment arrivesThe quality of the extracted cells varies depending on their health: Patients undergo chemotherapy to remove existing T cells before infusion, which provides a fresh canvas for the new cells but increases the chance of complications. Including life-threatening infections.
Fontana said that by avoiding chemotherapy, internal CAR-T could potentially improve outcomes, and eliminating the need for chemotherapy could broaden the range of applications of CAR-T.
There is growing interest in using this technology to treat autoimmune diseases. LupusCancer is caused by a malfunctioning immune system that mistakenly attacks healthy tissue, and CAR-T has shown dramatic results in some patients by stopping this immune system attack, putting the disease into drug-free remission.
However, risks associated with traditional CAR-T make it likely only an option for severely ill patients. Capstan aims to change that and treat more patients with its recently approved autoimmune candidate, the flagship in vivo CAR-T therapy, CPTX2309. $175 million in Series B funding.
Fontana said in vivo CAR-T also has the potential to democratize access to the treatment, giving developers access to a large underserved patient population. Only 20% of U.S. hospitals offer autologous CAR-T, meaning the majority of cancer patients, even those who could benefit, don’t have access to the treatment. In vivo therapies can be manufactured and stored at hospitals or distribution centers and could be easier to administer, allowing more facilities in the U.S. and abroad to offer the treatment.
At least one autologous transplant company is moving to overcome some of these logistical challenges: Gilead’s Kite Pharma, which makes Yescarta and Tecartas. Reduce manufacturing time Bringing CAR-T into more local oncology practices. TG Therapeuticsrecently obtained an allogeneic CAR-T candidate. Precision BioscienceIn the past, many have sought off-the-shelf therapies that use donor cells to speed up and improve the quality of treatment. Still, allogeneic therapies face unique challenges, such as keeping a patient’s immune system from attacking the foreign cells.
Facing the Challenge
In vivo CAR-T also faces challenges, including: Expanding production Therapeutic components such as genetically modified viruses and synthetic genetic material are being developed, and the field also needs to find the best technological approaches.
A handful of startups, including Ensoma and Exuma Biotech, are testing in vivo CAR technology using gene vectors such as lentiviruses and adeno-associated viruses, as well as non-viral platforms such as lipid nanoparticles and nanocarriers, according to Fran Gregory, vice president of emerging therapies at Cardinal Health.
Farzaneh Far believes Capstan’s delivery method, which uses lipid nanoparticles similar to those used in COVID-19 vaccines, may have an advantage over companies using viral vectors, which have safety concerns. Gregory said using viral vectors in the body can be toxic to the liver and brain and can cause thrombotic microangiopathy, a condition in which blood clots form in small arteries and capillaries.
“Non-viral vectors such as lipid nanoparticles or nanocarriers may be useful, but this is still under investigation,” she said.
Gregory said the success of the in vivo technology also depends on whether developers can find ways to mitigate adverse events, including those common to CAR-T, such as neurotoxicity and cytokine release syndrome.
“Developers also need to prevent off-target delivery and ensure that only target cells are affected,” she said.
Umoja is CD-22 molecule The company developed the molecule to test its technology and avoid the additional risks associated with an unknown target, and Fontana said the molecule has shown efficacy in people who have not responded to CD19-targeting CAR-T treatments such as Kymriah.
“Clearly, there’s an unmet medical need because there’s nothing being offered to these patients,” Fontana said. If the technology proves successful, it could open the door to new in vivo CAR-T indications, including solid tumors, Fontana said.
For now, the biggest hurdle for in vivo CAR-T is the unknown: While companies are seeing promising early results in nonhuman primates, monkeys are not human.
“If any of us prove that this works, it will dramatically change the field,” Fontana said. “The field has probably advanced more rapidly in the last two years than any other field I’ve seen.”
Fontana said next year will be pivotal and will reveal whether in vivo CAR T-cell therapy has transformative potential or whether further tweaks are needed.
“I’m sure by this time next year, at least some people will have the data,” he said.
