Sen­ti sci­en­tif­ic co-founder Wil­son Wong de­signs the SUPRA — a new, high per­for­mance mod­el CAR-T

Wil­son Wong, one of the sci­en­tif­ic co-founders be­hind Tim­o­thy Lu’s new syn­thet­ic bi­ol­o­gy start­up Sen­ti, has de­signed a new CAR-T that he be­lieves has the po­ten­tial to over­come some of the big is­sues that con­tin­ues to plague the first gen­er­a­tion of drugs now on the mar­ket.

And he’s tricked it out with some in­ter­est­ing new fea­tures.

The Boston Uni­ver­si­ty T-cell en­gi­neer — work­ing with grad­u­ate stu­dent Jang Hwan Cho and MIT’s Jim Collins, a leg­end in syn­thet­ic bio cir­cles and a men­tor to Lu — pub­lished a pa­per in Cell to­day out­lin­ing their work on the re­design, which Sen­ti will now see if it can guide to­ward the clin­ic.

Jim Collins

Work­ing with mouse mod­els, Wong de­vised a CAR he’s dubbed the SUPRA —  which stands for split, uni­ver­sal and  pro­gram­ma­ble. The cen­tral part of its promise is that the re­vised CAR-T is built to go af­ter two mark­ers for the dis­ease, vast­ly im­prov­ing its chance of ex­tend­ing the use of these drugs in­to hard-to-hit sol­id tu­mors while im­prov­ing the speci­fici­ty of the drug to can­cer tis­sue.

It’s al­so a cus­tomiz­able ap­proach, with bet­ter built-in con­trol fea­tures that can be used to go af­ter spe­cif­ic types of blood can­cer and sol­id tu­mors.

“What’s nice,” he tells me, “is that you need two sig­nals to turn on the T cells, not one mag­ic bul­let. The can­cer mark­er can be less spe­cif­ic, re­ly­ing on the in­ter­sec­tion of the two.”

The oth­er key in­gre­di­ent is an added adap­tive mol­e­cule which can be in­clud­ed with the treat­ment to guide the T cells to can­cer cells. With­out these adap­tive mol­e­cules, the T cell won’t be ac­ti­vat­ed, he says. And as they’re cleared even­tu­al­ly, you can add a fresh sup­ply to en­gi­neer a fresh re­sponse to a cho­sen tar­get.

Add it up and you gain a ba­sic on/off switch that can be used to fine tune the ac­tiv­i­ty of the ther­a­py to con­trol tox­i­c­i­ty, pre­vent­ing the kind of over­ac­tiv­i­ty that can launch a dan­ger­ous re­ac­tion in pa­tients. And you can more eas­i­ly spur a fol­lowup re­sponse to pre­vent re­laps­es.

It’s pre­clin­i­cal, which means there’s still plen­ty of work that would need to be done be­fore it could be test­ed in a hu­man. How long?

Maybe two years, says the sci­en­tist, “but you nev­er know.”

The first two CAR-Ts on the mar­ket, Yescar­ta and Kym­ri­ah, work ac­cord­ing to a sim­ple de­sign plan, tak­ing pa­tient cells, en­gi­neer­ing them with a chimeric anti­gen re­cep­tor, and then un­leash­ing a swarm to at­tack can­cer cells.

But it’s lim­it­ed, and not just by the tox­i­c­i­ty of an un­con­trolled re­ac­tion. The first gen­er­a­tion pa­tients are al­so ex­posed to re­laps­es as the ac­tiv­i­ty wears down, and adding a new half-mil­lion dol­lar ther­a­py isn’t fea­si­ble.

The long-term plan is to cre­ate an off-the-shelf ther­a­py with uni­ver­sal fea­tures for each can­cer type, and the re­searchers now are ze­ro­ing in on the types of can­cers which are most like­ly to re­spond to the two-tar­get de­sign.

The grand idea here is that Wong wants to build a “pros­thet­ic im­mune sys­tem,” a mas­ter con­trol tech­nol­o­gy that could pro­vide a new sys­tem that would gov­ern the im­mune re­sponse to any dis­ease, which would have a pow­er­ful and ob­vi­ous role to play on reg­u­la­to­ry T cells that sup­press an im­mune re­sponse as well as in au­toim­mune dis­eases like rheuma­toid arthri­tis. 

That’s a sub­stan­tial­ly big­ger vi­sion than the work on CAR-T 2.0. But these steps fol­low a longer path for Wong that he’s keen to ex­plore.

Im­age: Wil­son Wong. BOSTON UNI­VER­SI­TY

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Eisai and METAvivor plan to debut the latest 'This is MBC' campaign at the San Antonio Breast Cancer Symposium (SABCS).

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Moderna sued Pfizer and BioNTech back in August, alleging that the partners’ Covid-19 vaccine Comirnaty copied parts of Moderna’s vaccine technology patented before the pandemic, when it was developing an mRNA vaccine for MERS, another respiratory illness.

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Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

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Sum­i­to­vant sub­sidiaries En­zy­vant and Al­ta­vant merge in­to com­bined com­pa­ny

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Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

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