Re­searchers at City of Hope com­bine on­colyt­ic virus with a CAR-T to erad­i­cate sol­id tu­mors in mice

A new com­bi­na­tion of ex­ist­ing can­cer treat­ments is show­ing ear­ly signs of po­ten­tial­ly crack­ing open a new ap­proach to treat­ing sol­id tu­mors.

In pre­clin­i­cal re­search pub­lished by City of Hope, a Cal­i­for­nia-based non-prof­it, sci­en­tists ef­fec­tive­ly blend­ed CAR-T ther­a­py with an on­colyt­ic virus to erad­i­cate sol­id tu­mors in mice. The virus is ge­net­i­cal­ly en­gi­neered to en­ter the tu­mors and force them to ex­press the CD19 pro­tein, al­low­ing the CAR-T cells to at­tack.

Saul Price­man

“We came up with the idea based on the com­pat­i­ble ex­per­tise and es­sen­tial­ly with sev­er­al in­ves­ti­ga­tors at City of Hope,” Saul Price­man, se­nior au­thor of the pa­per, told End­points News. “It was al­most an idea to over­come the chal­lenges as­so­ci­at­ed with treat­ing sol­id tu­mors with CAR-T cell ther­a­py … the chal­lenge be­ing what tu­mor anti­gen to go af­ter in sol­id tu­mors and al­so what we call the im­muno­sup­pres­sive mi­croen­vi­ron­ment.”

The re­searchers are ex­pect­ing to move in­to hu­man tri­als with­in the next year and a half. Price­man added he likes to de­scribe the method as “mark and kill,” where the virus marks the tu­mor with a rec­og­niz­able tar­get for the CAR-T cells that then go in for the kill.

Nor­mal­ly used to treat blood can­cers like B cell lym­phomas and acute lym­phoblas­tic leukemia, CAR-T ther­a­py has made sig­nif­i­cant head­way since net­ting its first FDA ap­proval back in late 2017. The suc­cess seen in these can­cers hasn’t trans­lat­ed in­to sol­id tu­mors as of yet giv­en that find­ing re­cep­tors on the sur­faces of those cells is much more chal­leng­ing and can lead to un­want­ed tox­i­c­i­ties.

By com­bin­ing CAR-T with a virus that es­sen­tial­ly com­pels the tu­mors in­to ex­press­ing a re­cep­tor like CD19, how­ev­er, Price­man hopes this con­cept can be a game-chang­er. Specif­i­cal­ly in the mouse tri­als, Price­man and his team showed the virus was able to ex­press CD19 in triple-neg­a­tive breast can­cer, as well as in pan­cre­at­ic, prostate, ovar­i­an, and head and neck can­cer, as well as brain tu­mor cells.

On­colyt­ic virus­es have had marked­ly less suc­cess when used on their own to treat can­cers, ac­cord­ing to pa­per co-au­thor An­tho­ny Park, large­ly be­cause the im­mune sys­tem can de­vel­op a re­sis­tance. They’ve al­so nev­er been test­ed clin­i­cal­ly, but with CAR-T’s safe­ty pro­file al­ready well-known, the team is ex­pect­ing pos­i­tive re­sults.

When used alone, the on­colyt­ic virus “will in­duce an en­doge­nous im­mune re­sponse, which could be ben­e­fi­cial for tar­get­ing tu­mors, but it can al­so be detri­men­tal to the virus ac­tiv­i­ty be­cause the im­mune sys­tem can rec­og­nize the virus to not on­ly show the tu­mor cells but al­so get rid of the virus,” Park said.

Ezra Co­hen

City of Hope’s re­sults have al­ready im­pressed some out­side ex­perts, name­ly Ezra Co­hen, the chief of UC San Diego’s hema­tol­ogy-on­col­o­gy di­vi­sion. Co­hen, who him­self is re­search­ing a sim­i­lar com­bi­na­tion us­ing ROR1-tar­get­ing CAR-T cells, said City of Hope used a “clever ap­proach” and found an added bonus in the study when the virus prop­a­gat­ed in­to oth­er tu­mor cells af­ter the orig­i­nal­ly-in­fect­ed cells died off.

That could sug­gest wide­spread ef­fi­ca­cy even if the on­colyt­ic virus doesn’t man­age to in­fect every sin­gle tu­mor cell.

“You’ve got this ham­mer, which has been suc­cess­ful in hema­to­log­i­cal dis­eases, but you can’t use it for all the pa­tients with sol­id tu­mors be­cause you can’t see the nail,” Co­hen said. “But what City of Hope did is they put the nail in­to cells that they want­ed, and now all of a sud­den you can use that ham­mer and it be­comes ef­fec­tive.”

The biggest chal­lenge mov­ing for­ward will be how well the ex­per­i­ments in mice can trans­late in­to hu­mans. Some ex­per­i­men­tal CAR-T ther­a­pies have failed at this stage be­fore, Co­hen said, as get­ting the treat­ment to hone in on the tu­mor when it’s not di­rect­ly in­ject­ed in­to its cells — some­thing that’s not al­ways pos­si­ble in hu­mans with metasta­t­ic can­cers — is im­mense­ly dif­fi­cult.

But Price­man is con­fi­dent in the ex­per­tise of the City of Hope team, not­ing that the in­sti­tu­tion has 30 ac­tive Phase I clin­i­cal tri­als with CAR-T cells in a range of dis­eases.

“One of the beau­ties of City of Hope is we’ve done this a num­ber of times,” Price­man said. “Clin­i­cal trans­la­tion of a CAR-T cell is some­thing we have a wide ex­per­tise in, and we’ve al­so grow­ing ex­per­tise in on­colyt­ic virus­es.”

So­cial: Michael Dominguez, Shut­ter­stock

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

Pur­due Phar­ma pleads guilty in fed­er­al Oxy­Con­tin probe, for­mal­ly rec­og­niz­ing it played a part in the opi­oid cri­sis

Purdue Pharma, the producer of the prescription painkiller OxyContin, admitted Tuesday that, yes, it did contribute to America’s opioid epidemic.

The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

News brief­ing: Gilead part­ner Gala­pa­gos sells off CRO for $37M; Polyphor bags $3.3M from CF Foun­da­tion

Close Gilead ally Galapagos is selling off one of its contract research organizations to a Polish pharma company.

Galapagos has agreed to sell 100% of the outstanding shares in the CRO Fidelta to Selvita, in a deal worth roughly $37 million expected to close in the first week of January. The acquisition is expected to nearly double Selvita’s revenues, the company says, as well as expand its drug discovery efforts.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Michelle Longmire, Medable CEO (Jeff Rumans)

Med­able gets $91M for vir­tu­al clin­i­cal tri­als, bring­ing to­tal raise to $136M

As biotechs look to get clinical studies back on track amid the pandemic, Medable returned to the venture well for the second time this year, bagging a $91 million Series C to build out its virtual trial platform.

The software provider recently launched three new apps for decentralizing clinical trials, and saw a 500% revenue spike this year. And it isn’t alone. Back in August, Science 37 secured a $40 million round for its virtual trial tech, with support from Novartis, Sanofi Ventures and Amgen. Patients and researchers are taking a liking to the online approach, suggesting regulators could allow it to become a new normal even after the pandemic is over.