Approved just last year, CAR T-cell therapy is offering hope to patients with severe forms of blood cancer. The developer of one of only two CAR therapies currently in the market, Kite, has partnered with the Dutch Gadeta in order to support the development of a new type of CAR T-cells with several potentially breakthrough advantages, Labiotech reports.
While traditional CAR therapies are based on alpha beta T cells, the most common subtype of T cells, Gadeta focuses on a subtype known as gamma delta T cells. The main difference lies in the T-cell receptors (TCRs) that the immune cells use to recognize the target to attack.
“We use alpha beta T cells as a vehicle, with the TCR of a gamma delta T cell. That means that there is a whole new field of targets as opposed to the alpha beta T cells,” Gadeta’s CEO Shelley Margetson said.
The main advantage of these new targets is that they open up the possibility of using CAR-T cells to treat solid tumors, especially given that current forms of the therapy have shown limitations in their efficacy beyond “liquid” blood cancers.
Another advantage of gamma delta T cells is that they can recognize their target independently of the type of molecule that presents it.
“Therefore, it reacts much quicker than alpha beta T cells,” Margetson explained.
As part of the deal, Kite, which was acquired by Gilead for €10Bn last year, will fund the R&D of Gadeta. In exchange, it will acquire equity in Gadeta, which will be increased as certain milestones in the development of the technology are met. Kite will also have an exclusive option to acquire the company and its whole technology platform.
Gadeta is not the only company using gamma delta T cells to fight cancer. TC Biopharm and GammaDelta Therapeutics are also taking advantage of these unique immune cells, but Gadeta seems to be the only one combining the TCRs of gamma delta T cells with alpha beta T cells.
“Gadeta is the most advanced company of receptor-specific gamma delta T cells,” said Giovanni Mariggi, Principal of the investment firm Medicxi. “We are very happy that someone of the caliber of Kite supports a company that we created as founding investors.”
“I think someone who is that experienced in the cell therapy field will help us advance our technology faster and more efficiently and hopefully get our technology into solid tumors,” agreed Margetson.
One of my siblings is acquainted with a woman, let’s call her Lani, who battled metastatic breast cancer here in the US for many years. There were countless rounds of chemotherapy and surgery, but this past December she was told by her oncology team that all of their, and her, efforts had led them to classify her “terminal,” with approximately 6 weeks of life left.
Lani, in effect, said, “6 weeks my keister,” and off she went to Germany where she underwent CAR T-cell therapy for 3 months. Now she’s back in the States and back to the work she loves, feeling better than she can’t remember. And she’s in her mid-60’s!
Why am I bringing this up? It’s because CAR T apparently works on solid tumors as well as the liquid cancers. Yes, Kite and Gadeta’s approach is still very experimental. And the science surrounding many cancer treatments, such as gastric signet-ring cell carcinoma and immunotherapy, is “evolving,” say the clinicians. But when you’ve been told that a complete gastrectomy (removal of the entire stomach) and more rounds of highly toxic platinum-based chemo is your only option, what other choices are there?
With Lani, “terminal” didn’t belong in her lexis. She simply was not yet ready to give up the fight. She’s in remission. Yes, her cancer can return. But she’s already got the majority of her former, “normal” life back and is happy she fought on.
Turning to the Kite/Gadeta story above, Europe may be late to the I/O party, but it’s leading the way with a protocol that benefits all, not just the rich.
The EU-funded project–Chimeric Antigen Receptors (CARs) for Advanced Therapies (CARAT)–aims to develop a new, comprehensive platform for innovative cell manufacturing technologies as part of the European Horizon 2020 research and innovation program.
From the US and European perspective, CAR T-cell therapies pose enormous opportunities, perhaps someday eclipsing blockbuster checkpoint inhibitors such as Merck & Co.’s Keytruda and Bristol-Myers’ Opdivo. In fact, CAR T-cell is emerging as an even more effective approach that just might become “standard of care” in certain indications. Recently, clinical trials resulted in impressive response rates as high as 60–85% in patients with various lymphomas and leukemias of B-cell origin.
Furthermore, these new therapies imply considerable financial returns. For instance, Seattle-based Juno Therapeutics is one of the most conspicuous start-up companies developing CAR therapies. The US founders were able to raise more than $300 million in funding in less than 12 months. Juno and other examples illustrate why cellular therapy is regarded by renowned financial market analysts as a multi-billion-dollar industry.
Analysts say European healthcare systems would benefit in terms of the improved cost-effectiveness of CAR therapies. Conventional cancer therapies are often at least 2-3 times more expensive than cellular CAR therapy, which is estimated to cost 50,000-70,000 Euro. Therefore, not only will patients benefit from CARAT but so will the pharmaceutical industry and healthcare providers.
However, in Europe, despite the extraordinary opportunities for patients, healthcare providers and the pharma industry, there are demanding challenges ahead. Most of all, there is already strong international competition for personalized cellular therapies. The majority of the trials take place in the US. However, China is catching up and Europe is in danger of being left behind.Steve's Take: Financing CAR for all will be fraught with the usual political warfare, but in the end, shouldn’t we all have access to CAR treatment through some form of insurance? Click To Tweet
Despite the success of Novartis’s Kymriah and Gadeta’s new approach for solid tumors, CAR therapy is a fledgling discipline. There are limitations and hurdles to overcome before it will be established as a standard treatment in clinic.
A broader implementation strongly depends on the development of T-cell manufacturing processes that are robust and scalable. This would make T-cell therapies more accessible, in part by attracting interest from commercial entities, who would ultimately transform adoptive T-cell transfer from “boutique” to “chain store.”
Given the need to reach a wider dissemination of CAR T-cell therapies, what are the basic requirements to optimize manufacture of a gene-modified cellular therapy product?
CARAT’s central working hypotheses, which I fully endorse, can be summarized as follows:
1) The process should be simplified as much as possible to reduce workload and increase productivity. Importantly, the process must be robustly reproducible to eliminate failure risks and enable standardization.
2) It should be cost effective and scalable to enhance product commercialization and availability for patients that need them. Especially the integrity and sterility of the process needs to be addressed, since the cultivation of the cells may take several days to weeks.
3) The manufacturing process must result in a safe and clinically effective cell product for the patient and should meet all regulatory requirements.
Simple, clean and a model program for us to adapt to our healthcare delivery system here in the US. Financing CAR for all will be fraught with the usual political warfare, but in the end, shouldn’t we all have access to CAR treatment through some form of insurance? Especially if it turns out to be a single-dose cure?