Connect with us

Economics

Updates on gene therapy for ‘bubble boy’ disease and cellular immunotherapy at ASGCT

(MEMPHIS, Tenn. – May 12, 2022) Interim results of an ongoing clinical trial found lentiviral gene therapy is safe and effective for treatment of infants…

Published

on

(MEMPHIS, Tenn. – May 12, 2022) Interim results of an ongoing clinical trial found lentiviral gene therapy is safe and effective for treatment of infants with X-linked severe combined immunodeficiency (X-SCID). The report will be presented during the 25th annual meeting of the American Society of Gene and Cell Therapy (ASGCT). The conference will take place in person and virtually May 16 – 19, 2022 at the Walter E. Washington Convention Center in Washington, D.C.

Credit: Courtesy of St. Jude Children’s Research Hospital

(MEMPHIS, Tenn. – May 12, 2022) Interim results of an ongoing clinical trial found lentiviral gene therapy is safe and effective for treatment of infants with X-linked severe combined immunodeficiency (X-SCID). The report will be presented during the 25th annual meeting of the American Society of Gene and Cell Therapy (ASGCT). The conference will take place in person and virtually May 16 – 19, 2022 at the Walter E. Washington Convention Center in Washington, D.C.

 

“All of our patients are doing very well,” said Ewelina Mamcarz, M.D., of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. “At a median follow up of over two and a half years, the therapy appears to be safe and effective. The patients develop functional immune systems with no evidence of abnormal cell division.”

 

X-SCID, also known as bubble boy disease, is a rare, life-threatening disorder caused by a mutation in a single gene that prevents proper immune function. In 2019, St. Jude published an initial report in the New England Journal of Medicine documenting the success of the gene therapy developed and produced at St. Jude. Thursday, May 19, at 8:45 a.m. ET, Mamcarz will present interim results for the first 23 patients treated in the multi-center clinic trial.

 

The ASGCT annual meeting is a venue for professionals in gene and cell therapy to display their work with colleagues. The meeting serves a wide community, including academic researchers, clinicians, bio-industry developers, regulatory agencies, equipment manufacturers, patient advocates and others. The meeting will also feature other St. Jude scientists discussing research related to immunotherapies using chimeric antigen receptor (CAR) T cells from the Krenciute, Velasquez, Zhang and Gottschalk laboratories and immune response to vectors from the Davidoff laboratory.

 

Oral presentations preview

  • St. Jude researchers will give three presentations during a session titled “CAR T cells and Beyond.” Jaquelyn Zoine, Ph.D., Bone Marrow Transplantation and Cellular Therapy, will give two presentations. First, she will discuss how naturally occurring CD7- T cells mark a more effective and long-life CAR T cell population. The talk is Monday, May 16, at 4:30 p.m. ET. Zoine will reveal how CAR T cells without a certain protein have robust antitumor activity against the most common type of childhood cancer.
  • At 5 p.m. ET, Zoine will discuss bispecific CAR T Cells targeting AML. She is the first to show that a novel hybrid targeting molecule, including both a signaling chain variant that binds one target and a peptide that binds another target, improves tumor clearance and prevents immune escape.

At 5:15 p.m. ET, Dalia Haydar, Ph.D., Bone Marrow Transplantation and Cellular Therapy, will discuss a CAR T cell with superior efficacy in an immune competent brain cancer model. Haydar is the first to test the function of different CAR domains in an immunocompetent model of a brain tumor. Haydar will show which domains worked best in this model. Haydar will also reveal the type of cells that are recruited into brain tumors to suppress the anti-cancer therapy.

 

  • Two St. Jude researchers are scheduled to participate in the “CAR T cell Efficacy” session. Matthew Bell, a Ph.D. candidate in the St. Jude Graduate School of Biomedical Sciences, will discuss his work engineering a more effective CAR T cell immunotherapy for solid tumors. The talk is Tuesday, May 17, at 3:45 p.m. ET. CAR T cells have not been as effective for solid tumors due to problems with expansion and persistence. Bell’s work focuses on how to extend CAR T cell survival.

 

Brooke Prinzing, Ph.D., Department of Bone Marrow Transplantation and Cellular Therapy, will discuss chimeric switch receptors that improve CAR T cell antitumor activity. The talk is Tuesday, May 17, at 5 p.m. ET. This research demonstrates how to enhance antitumor of CAR T cells.

 

  • Elizabeth Wickman, a Ph.D. candidate in the St. Jude Graduate School of Biomedical Sciences, will discuss a potential target for CAR T cells in the immunotherapy of pediatric brain and solid tumors. The talk is Wednesday, May 18, at 4:30 p.m. ET in a session titled “Cell-based Cancer Immunotherapies II.” Solid and brain tumors have a limited set of targetable antigens for CAR T cell therapies. Wickman’s work has identified a potential antigen which they then used to create a CAR T cell strategy with some effect in vivo for osteosarcoma.

 

  • During the “Cell Therapy Product Engineering, Development or Manufacturing” session, Jorge Ibañez-Vega, Ph.D., Bone Marrow Transplantation and Cellular Therapy, will discuss how dysfunctional immune synapses restrain anti-DIPG activity of CAR T cells. The talk is Thursday, May 19, at 11:30 a.m. ET. Ibañez-Vega will show how hard to treat brain tumors suppress CAR T cell effector functions by contributing to the formation of dysfunctional immune synapses.

Featured New Technologies

  • Mark Brimble, Ph.D., Immunology, will discuss transcription, translation, and immunogenic potential of rAAV contaminants post-infection during a session titled “Discoveries in Fundamental AAV Biology.” The talk is Tuesday, May 17, at 4:15 p.m. ET. Recombinant adeno-associated virus (rAAV) preparation includes using plasmids that can be packaged into vectors. Brimble will explain an innovation to decrease DNA contaminants while maintaining vector yields.

 

Awards and more

Stephen Gottschalk, M.D., chair of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will chair the workshop “Immune Effector Cell Therapies” on Sunday, May 15, 1 – 4:40 p.m. ET. The workshop includes a 2:50 p.m. ET talk by Giedre Krenciute, Ph.D., Bone Marrow Transplantation and Cellular Therapy, titled “Gene editing to improve CAR T cell therapy.”

 

Haydar will receive an Excellence in Research Award for his abstract featuring a novel CAR T cell with superior efficacy in an immune competent brain cancer model during the George Stamatoyannopoulos Lecture. The event is Wednesday, May 18, at 10:15 am. ET. His abstract was selected as one of the top 18 that postdoctoral fellows or students submitted.

 

X-SCID gene therapy interim results

 

Mamcarz will present the interim status of the trial, the largest cohort of infants with X-SCID, who have received gene therapy. Over half of the infants in this report look immunologically like their peers, while the remaining patients appear to be following the pattern of immune recovery of their predecessors but are currently early post therapy. While the median follow-up is two and a half years, six patients are at or near the milestone of being five years post therapy.

 

“All patients have functional immune cells post gene therapy,” Gottschalk said. “These results look and continue to be very encouraging. However, there are very few studies where patients have gotten gene therapy so early in life, so we need to continue to observe these children.”

 

So far, the treatment appears safe and yields a stable, functioning immune system. There has been no sign of leukemogenesis.

 

“These patients get regular pediatric infections, and they recover from them,” Mamcarz said. “There were several patients who had COVID-19, RSV or flu infections and fought them off without any issues.”

 

St. Jude researchers have partnered with Mustang Bio, a biotech company that is seeking U.S. Food and Drug Administration approval for the St. Jude gene therapy approach for X-SCID.

 

St. Jude Media Relations Contacts

Michael Sheffield
Desk: (901) 595-0221
Cell: (901) 275-9065
michael.sheffield@stjude.org
media@stjude.org

 

Emily Gest 

Desk: (901) 595-0260 

Cell: (901) 568-9869 

emily.gest@stjude.org 

media@stjude.org 

 

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.

 

 


Read More

Continue Reading

Economics

Hotels: Occupancy Rate Down 3.5% Compared to Same Week in 2019

From CoStar: STR: Weekly US Hotel Revenue per Available Room Reaches Highest Level Since July 2019U.S. hotel performance increased from the previous week, according to STR‘s latest data through May 21.May 15-21, 2022 (percentage change from comparable …

Published

on

U.S. hotel performance increased from the previous week, according to STR‘s latest data through May 21.

May 15-21, 2022 (percentage change from comparable week in 2019*):

Occupancy: 68.6% (-3.5%)
• Average daily rate (ADR): $151.75 (+13.4%)
• Revenue per available room (RevPAR): $104.06 (+9.5%)

*Due to the pandemic impact, STR is measuring recovery against comparable time periods from 2019.
emphasis added
The following graph shows the seasonal pattern for the hotel occupancy rate using the four-week average.

Click on graph for larger image.

The red line is for 2022, black is 2020, blue is the median, and dashed light blue is for 2021.  Dashed purple is 2019 (STR is comparing to a strong year for hotels).

The 4-week average of the occupancy rate above the median rate for the previous 20 years (Blue).

Note: Y-axis doesn't start at zero to better show the seasonal change.

The 4-week average of the occupancy rate will mostly move sideways seasonally until the summer travel season.

Read More

Continue Reading

Economics

“This Is A Crucible Moment” – Sequoia’s Ominous Warning To Companies On How To “Avoid The Death Spiral”

"This Is A Crucible Moment" – Sequoia’s Ominous Warning To Companies On How To "Avoid The Death Spiral"

"This is not a time to panic. It is…

Published

on

"This Is A Crucible Moment" - Sequoia's Ominous Warning To Companies On How To "Avoid The Death Spiral"

"This is not a time to panic. It is a time to pause and reassess," begins the thought-provoking presentation from veteran venture capital firm Sequoia Capital.

But that's about as 'positive' as they get as the founders of the firm warn of a prolonged market downturn and urges the startups in its portfolio to preserve cash and brace for worse to come.

"We believe this is a Crucible Moment, one that will present challenges and opportunities for many of you. First and foremost, we must recognize the changing environment and shift our mindset to respond with intention rather than regret."

And in its somewhat ubiquitous historically grim outlooks (its "R.I.P Good Times" in 2008 and "Black Swan" memo in March 2020 have become legendary) don't expect a quick rescue and recovery this time.

"Sustained inflation, and geopolitical conflicts further limit the ability for a quick-fix policy solution. As such, we do not believe that this is going to be another steep correction followed by an equally swift V-shaped recovery, like we saw at the outset of the pandemic," the note said.

They argue that it will be "Survival of the Quickest"...

In particular, Sequoia urged companies to look at cutting projects, R&D, marketing, and other expenses, noting that companies should be ready to cut in the next 30 days.

"We expect the market downturn to impact consumer behaviour, labour markets, supply chains and more. It will be a longer recovery and while we can't predict how long, we can advise you on ways to prepare and get through to the other side," it said.

The founders/CEOs who face reality, adapt fast, have discipline rather than regret will not just survive, but win, noting that "It is easier to preserve cash when you have more than six months left. Recruiting is about to get easier. All the FANG have hiring freezes."

They conclude their presenttation by noting that:

"At Sequoia, we believe that the one who wins is the one most prepared."

In other words America, brace for capex cuts, hiring freezes to accelerate, and growth to evaporate.

*  *  *

Read the full presentation below:

Tyler Durden Thu, 05/26/2022 - 15:45

Read More

Continue Reading

Economics

Best Day For Discretionary Stocks Since COVID-Crash As Consumer Recession Bets Get Steamrolled

Best Day For Discretionary Stocks Since COVID-Crash As Consumer Recession Bets Get Steamrolled

A week ago, following dismal guidance by Walmart,…

Published

on

Best Day For Discretionary Stocks Since COVID-Crash As Consumer Recession Bets Get Steamrolled

A week ago, following dismal guidance by Walmart, Target indicated that it is seeing a shift in the consumer wallet away from the pandemic purchases and into reopening purchases - including apparel - and the pace of this shift caught some retailers off guard on inventory. WMT, COST, and TGT all saw their stocks fall sharply last week as investor concerns around a US consumer slowdown mounted and investors reconsidered just where, if anywhere, you can play "defense" in the current market.

But as Goldman's Chris Hussey writes today, this week, results from companies like DKS, Macy's, JWN, WSM, DLTR, and DG painted a decidedly different picture.

Deep discount retailers Dollar Tree - or rather Dollar 25 Tree - and Dollar General both posted strong results and DLTR raised top-line guidance.

Which isn't surprising: as we discussed in "Middle Class Is Shutting Down As Spending By The Rich Remains Robust" when consumers are trading down - as they are doing now due to Biden's runaway inflation - dollar stores see more business.

As a result, Dollar Tree surged as much as 20% on Thursday, the biggest intraday move since October 2020. Evercore ISI said Dollar Tree's move to a "$1.25 price point" last November from $1 “came in the nick of time" adding that "given the broad-based inflationary cost pressures, the 25% price increase drove material sales and margin upside for both the namesake division and the total company," wrote analyst Michael Montani who also said that while freight, transport, and labor headwinds are real, some of the pressure cited by Target last week was likely company specific.

The analyst concluded that the read-across from DG and DLTR is “favorable,” and it seems that the low-end consumer is “hanging in better than initially thought.” Or rather, the middle-class is getting crushed and it has no choice but to trade down to the cheapest retail outlets.

And with countless shorts having piled up and getting massively squeezed, the S&P 500 Consumer Discretionary Index today has risen as much as 5.6%, its best day since April 2020, as optimism on the health of the consumer returns following a string of better-than-expected earnings reports from retailers.

Top performers in the S5COND index include Dollar Tree, Dollar General, Norwegian Cruise, Caesars Entertainment and Carnival; the Discretionary Index is on pace for its best week since March 18, when the group climbed 9.3%; the index sank 7.4% as Walmart and Target reports spooked investors. The index is still down almost 30% YTD.

"Retail earnings are bullish.... with four blow-outs,” said Vital Knowledge’s Adam Crisafulli, referring to quarterly reports from Williams-Sonoma, Macy’s, Dollar General, and Dollar Tree.  “The overall retail industry is experiencing stark changes and the market is incorrectly conflating these shifts with underlying demand weakness when the actual health of the consumer is much better than it seems,” Crisafulli says, although there are many - this website included - who wholeheartedly disagree with his optimistic view of the US consumer.

Remarkably, thanks to today’s rally, even Burlington Stores, which sank as much as 12% in premarket on disappointing results, is trading up as much as 11% and some say, the rally helped reverse the earlier tumble in NVDA shares.

The discretionary group is also getting a boost from airline operators Southwest and JetBlue, helping travel-related names, while on the economic front, better-than-expected personal consumption (for the revised Q1 GDP print). and jobless claims may be adding to the bullishness according to Bloomberg.

Tyler Durden Thu, 05/26/2022 - 15:00

Read More

Continue Reading

Trending