Darrell Irvine. MIT

Su­per­charg­ing CAR-T with can­cer vac­cine, MIT team spot­lights some new tech un­der­pin­ning Dar­rell Irvine's start­up

Many of the ef­forts to im­prove on the first gen­er­a­tion of CAR-T ther­a­pies such that they can reach sol­id tu­mors had fo­cused on tweaks in­her­ent to the can­cer-killing agent — specif­i­cal­ly, uti­liz­ing more po­tent T cells as their base, from stem mem­o­ry T cells to vi­ral­ly as­so­ci­at­ed T cells to mar­row in­fil­trat­ing lym­pho­cytes. But what if just am­pli­fy­ing CAR-T cells can do the job? Dar­rell Irvine and his team at MIT have some in­trigu­ing mouse da­ta for one such tech.

Leyuan Ma Irvine Lab

Writ­ing in Sci­ence, Irvine — an in­ves­ti­ga­tor at the Koch In­sti­tute for In­te­gra­tive Can­cer Re­search — and his post­doc Leyuan Ma de­scribes “am­phiphile CAR-T lig­ands (amph-lig­ands) that, up­on in­jec­tion, traf­ficked to lymph nodes and dec­o­rat­ed the sur­faces of anti­gen-pre­sent­ing cells, there­by prim­ing CAR-Ts in the na­tive lymph node mi­croen­vi­ron­ment.” Among mice giv­en the boost­er shot af­ter CAR-T in­fu­sion, 60% ex­pe­ri­enced a com­plete re­sponse for a va­ri­ety of tu­mors in­clud­ing glioblas­toma, breast and melanoma. In con­trast, bare­ly any­thing hap­pened to those giv­en just the cell ther­a­py.

It rep­re­sents a twist to the once-hot — but elu­sive — can­cer vac­cine ap­proach, whose premise is to in­duce an im­mune at­tack on tu­mor cells. It al­so promis­es to solve the dura­bil­i­ty prob­lem of CAR-T that many re­searchers have high­light­ed.

“This is a strat­e­gy that can be as­signed to any CAR-T cell and po­ten­tial­ly en­hance its func­tion,” he tells me, ren­der­ing it ex­po­nen­tial­ly more po­tent. “So what­ev­er oth­er strat­e­gy they might be tak­ing en­gi­neer­ing bet­ter CARs, build­ing in oth­er ge­net­ic pay­loads in­to the T cells, this would be a way to make those cells more func­tion­al in vi­vo.”

By send­ing a vac­cine di­rect­ly to the lymph nodes to stim­u­late CAR-T cells, he ex­plains, they hit two birds with one stone: Pre­vent­ing vac­cines from get­ting de­grad­ed and CAR-T cells from re­leas­ing tox­ic cy­tokines — both of which hap­pen in blood­streams. And it com­bines the promis­es of both ther­a­pies.

“If we take the an­i­mals that ap­pear to be cured and we rechal­lenge them with tu­mor cells, they will re­ject all of them,” Irvine said in an in­ter­view with MIT News. “That is an­oth­er ex­cit­ing as­pect of this strat­e­gy. You need to have T cells at­tack­ing many dif­fer­ent anti­gens to suc­ceed, be­cause if you have a CAR-T cell that sees on­ly one anti­gen, then the tu­mor on­ly has to mu­tate that one anti­gen to es­cape im­mune at­tack. If the ther­a­py in­duces new T-cell prim­ing, this kind of es­cape mech­a­nism be­comes much more dif­fi­cult.”

To de­liv­er the amph-lig­ands, the sci­en­tists tagged on a lipid tail that binds to al­bu­min in the blood­stream and fol­lows it to the lymph nodes. Once there, the anti­gen in­side the vac­cine — ei­ther the same one the CAR-T is orig­i­nal­ly en­gi­neered to rec­og­nize or an­oth­er, they test­ed both — su­per­charges T cells and spurs their pro­lif­er­a­tion.

Irvine is hope­ful about con­duct­ing first-in-hu­man tri­als with­in one to two years through Eli­cio Ther­a­peu­tics, the sec­ond biotech he co-found­ed. In ad­di­tion to go­ing af­ter sol­id tu­mor in­di­ca­tions, he al­so sees ap­pli­ca­tion of his am­pli­fied CAR-T in the more tra­di­tion­al CD19 and BC­MA set­tings, as well as de­ploy­ing the vac­cine can­di­date alone for KRAS-mu­tant can­cers.

Eli­cio launched ear­li­er this year with $30 mil­lion in fund­ing, Robert Con­nel­ly (old-timers may re­mem­ber him as found­ing CEO of Do­man­tis) as chief and Gami­da Cells’ Ju­lian Adams as ex­ec­u­tive chair­man. The com­pa­ny is in talks with part­ners that might bring their own CAR-T to the ta­ble.

“Part of the beau­ty of this is,” he adds, “in the grand scheme of things, it will add noth­ing to the cost of CAR-T cell ther­a­py be­cause [it’s] es­sen­tial­ly a de­fined mol­e­c­u­lar en­ti­ty that can be made at scale pret­ty sim­ply.”

The re­search pub­lished to­day was par­tial­ly fund­ed by J&J — along­side the NIH, the Mar­ble Cen­ter for Can­cer Nanomed­i­cine and the Na­tion­al In­sti­tute of Gen­er­al Med­ical Sci­ences. Irvine said the phar­ma gi­ant is not cur­rent­ly an in­vestor, though it has been in touch.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Castle Creek Biosciences chair Jeff Aronin

Scoop: Af­ter pulling IPO am­bi­tions last De­cem­ber, Jeff Aron­in's Cas­tle Creek turns to pri­vate back­ers

Jeff Aronin’s cell and gene therapy biotech Castle Creek Biosciences has raised $112 million in equity, Endpoints News has learned.

The Exton, PA, biotech secured the financing from 54 investors, according to an SEC filing dated May 2. The late-stage startup had last year considered a $100 million Nasdaq debut, but in a sign of the bear market that has plagued hundreds of newly minted public biotechs, Castle Creek pulled those ambitions in the last few weeks of 2021.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.