Tar­get­ing CD47? UCLA joins band­wag­on, with gel to stem tu­mors from resur­fac­ing

Hit­ting the “don’t eat me” CD47 re­cep­tor tar­get has gal­va­nized an army of drug de­vel­op­ers who want to make in­roads in the bur­geon­ing field of can­cer im­munother­a­py by off­set­ting im­muno­sup­pres­sion. But in an ef­fort to sub­vert side ef­fects that can be caused by the sys­temic ab­sorp­tion of such an­tag­o­nists, re­searchers are test­ing a gel that could be sprayed on pa­tients who have un­der­gone surgery to in­hib­it tu­mor re­cur­rence and metas­ta­sis.

A biodegrad­able fib­rin gel, which en­cap­su­lates cal­ci­um car­bon­ate nanopar­ti­cles pre-loaded with an an­ti-CD47 an­ti­body, was used by a team of re­searchers led by Zhen Gu, a pro­fes­sor of bio­engi­neer­ing at the UCLA Samueli School of En­gi­neer­ing. Fol­low­ing tu­mor re­sec­tion in mice with ad­vanced melanoma, the gel was sprayed on to the sur­gi­cal site to cur­tail the growth of tu­mor cells that lin­gered de­spite surgery. Half the mice in the study did not see their tu­mors re-emerge 60 days fol­low­ing treat­ment, da­ta showed.

Zhen Gu

Cal­ci­um car­bon­ate — the main com­po­nent of egg shells — was cho­sen due to its abil­i­ty to be grad­u­al­ly dis­solved in sur­gi­cal wound sites, which are slight­ly acidic, and be­cause it boosts macrophage ac­tiv­i­ty, said the study’s lead au­thor Qian Chen, a post­doc­tor­al re­searcher at UCLA.

A pletho­ra of drug de­vel­op­ers in­clud­ing Alexo Ther­a­peu­tics, Arch On­col­o­gy, Au­ri­gene, Blink Bio­med­ical, Cel­gene, Forty Sev­en, Novim­mune, OSE Im­munother­a­peu­tics, Sor­ren­to, Syn­thon Hold­ing and Tril­li­um Ther­a­peu­tics, are de­vel­op­ing CD47 an­tag­o­nists in the hope of scram­bling the “don’t eat me” sig­nal that can­cer cells are de­pen­dent on to evade macrophages.

Qian Chen

But the oc­cur­rence of ane­mia and throm­bo­cy­tope­nia caused by sys­temic ad­min­is­tra­tion of such an­tag­o­nists-in-de­vel­op­ment re­mains a con­cern, the UCLA team wrote in their peer re­viewed study pub­lished in Na­ture Nan­otech­nol­o­gy.

Many can­cer pa­tients un­der­go surgery to up­root tu­mors, but of­ten the can­cer re-emerges. This re­search sug­gests the im­munother­a­peu­tic fib­rin gel can “awak­en” the im­mune sys­tem by re-arm­ing macrophages at the sur­gi­cal site to chew up can­cer cells.

“We al­so learned that the gel could ac­ti­vate T cells in the im­mune sys­tem to get them to work to­geth­er as an­oth­er line of at­tack against lin­ger­ing can­cer cells,” Chen added in a state­ment.

The team of sci­en­tists in­tends to test this ap­proach in an­i­mal tri­als to de­ter­mine the ide­al mix of nanopar­ti­cles, op­ti­mal dos­ing and treat­ment fre­quen­cy, be­fore grad­u­at­ing to hu­man test­ing.


At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; 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.

The slate of products we’re offering here at Endpoints is continuing to grow, and it’s not just limited to editorial. If you haven’t, do visit your reader profile to see if there are any other weekly newsletters you’re interested in — as each comes with its own exclusive content. And don’t miss the publisher’s note from Arsalan Arif on Endpoints Studio, our latest avenue for advertising on Endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Glax­o­SmithK­line, Ox­ford un­veil new part­ner­ship pit­ting buzzy R&D ad­vances against neu­ro­log­i­cal dis­ease

When GlaxoSmithKline trumpeted its return to neuroscience with a $700 million upfront deal with Alector this summer, it touted its early investments in functional genomics as a key guidepost for that deal. Now, the drug giant has partnered up with Oxford to hopefully add jet fuel to its hunt for breakthroughs in the brain.

GSK and Oxford have kickstarted a five-year collaboration aimed at spurring R&D breakthroughs across a range of hard-to-treat diseases like Alzheimer’s and Parkinson’s through the use of genomic testing and machine learning, the partners said Wednesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.