Because AML originates in the bone marrow and cancerous cells can “hide” there to escape chemotherapy treatment, the team analyzed the mice’s bone marrow. They found large numbers of active T cells and no trace of AML cells in the cryogel-vaccinated mice’s marrow. When they transplanted bone marrow from those mice into healthy mice that were then challenged with AML cells, all of the transplant recipients survived while a control group of mice succumbed to AML within 30 days, indicating that the immune protection against AML was sustained and transferable.Unexpected results, better-than-expected outcomesTo more closely mimic the clinical scenario of a human patient developing AML, the team injected their cryogel vaccine into mice that had AML along with the standard chemotherapy regimen that AML patients receive, which causes fast-dividing AML cells to die in large numbers. The activated T cell response in mice that received the combo therapy was six-fold higher than in mice that received chemo plus a traditional liquid vaccine, suggesting that the cryogel was a much more effective vehicle for delivering the activating biomolecules to the immune system.To test the durability of the immune response generated by the combo treatment, they harvested bone marrow from mice that were given the cryogel vaccine with WT-1 peptide along with chemotherapy and transplanted it into healthy mice. None of the recipient mice developed AML for up to 14 days after transplant, indicating that the combo-treated donor mice did not have residual AML cells in their marrow. All the recipient mice also survived a later challenge with AML cells, while mice that did not receive donor bone marrow died within 31 days.But, when the researchers started to tinker with the vaccine’s components to investigate why it worked so well, they saw something completely unexpected: vaccines that had no AML antigen in them were just as effective at providing protection as vaccines containing either AML cell contents or WT-1 peptide.“We were definitely surprised and really didn’t expect this result, because we initially thought that including the antigen in the vaccine was critical. That led us down some research avenues we hadn’t previously considered to try and understand what was going on,” said co-first author Alex Najibi, a graduate student in the Mooney lab. “We found that AML cells actually enter the cryogels over time, right where dendritic cells are already concentrated and activated. When the chemo causes large numbers of AML cells to die, the dendritic cells can pick up their remains as antigens and generate a strong signal to activate T cells against AML.”To further evaluate the efficacy of their antigen-free vaccine and chemotherapy combo, the team analyzed the bone marrow of mice with AML that received either the combo or the antigen-free vaccine alone. They found that the antigen-free vaccine alone did not effectively reduce the amount of AML cells in the marrow or increase the number of active T cells, but the combo therapy achieved both of those goals. The combo also caused a decline in the number of regulatory T cells (Tregs) in the marrow, which suppress immune function and are thought to be a major reason why AML cells in the marrow can evade immune detection.Work on the cryogel vaccine is continuing along multiple threads of inquiry. Mooney’s team is examining how it could be combined with sequencing technology to identify antigens that are specific to a single patient’s cancer and create a highly personalized vaccine, and also exploring potential synergies with T cell and other adoptive transfer techniques. Other members of the lab are researching antigen-free vaccines in the context of breast cancer, as well as further investigating the response they observed in AML.“We are very excited about the performance of our AML vaccine, because it could finally provide long-term, relapse-free survival for AML patients, either to ‘clean up’ residual AML cells in the bone marrow following a stem cell transplant, or in older patients who cannot tolerate either transplants or high-dose chemo,” said Mooney, who is also the Founding Core Faculty & Lead of the Immuno-Materials platform at the Wyss Institute at Harvard University and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.Additional authors of the paper include Ting-Yu Shih and Angelo Mao from the Wyss Institute and SEAS, and David Scadden and Azeem Sharda from the Department of Stem Cell and Regenerative Biology at Harvard University and the Harvard Stem Cell Institute.This research was supported by the National Institutes of Health, the Cancer Research Institute, and the National Science Foundation. Acute myeloid leukemia (AML) is a deadly blood cancer that originates in the bone marrow and kills most of its victims within five years. Chemotherapy has been the standard AML treatment for over 40 years, and while it often causes the cancer to go into remission, it rarely completely eliminates the cancerous cells, which then lead to disease recurrence in nearly half of treated patients. Aggressive post-remission treatments, like high-dose chemotherapy or bone marrow transplants, can reduce the chance of recurrence, but many AML patients are not healthy enough to tolerate them.Now, a new study presents an alternative treatment that has the potential to eliminate AML cells completely: an injectable, biomaterial-based vaccine that, when combined with standard chemotherapy, caused complete and lasting recovery from and immunity against AML in mice. The study was conducted by researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering, the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and the Harvard Stem Cell Institute (HSCI), and is published in Nature Biomedical Engineering.“We have previously developed cancer vaccines against solid tumors, and we were curious to see if this technology would also be effective at treating a blood cancer like AML,” said co-first author Nisarg Shah, a former postdoctoral fellow in the lab of Wyss core faculty member David Mooney, who is now an assistant professor at the University of California, San Diego. “The promising outcomes of the combination of this vaccine with chemotherapy may translate to human vaccines that can be personalized yet offer off-the-shelf convenience.”A crafty cryogelLike other vaccines, the AML vaccine “teaches” the body’s immune system to recognize a foreign invader (in this case, AML cancer cells) so that it can mount an effective attack when that invader appears. While traditional vaccines are typically liquid, this vaccine is a tiny, disk-shaped “cryogel” scaffold made primarily of two materials – polyethylene glycol and alginate – that have been cross-linked together to form a matrix. Two biomolecules (GM-CSF and CpG-ODN) are embedded in the scaffold to attract the body’s dendritic cells and activate them, along with antigens specific to AML cells (either contents from dead AML cells or a peptide from the protein WT-1 that AML cells express on their surface). The activated dendritic cells take up the antigens from the vaccine site and present them to T cells, triggering them to seek and destroy AML cells and, hopefully, patrol the body long-term to destroy any disease recurrence.To test whether their cryogel vaccine effectively primed the immune system to attack AML cells, the team injected it under the skin of healthy mice, and saw that it resulted in a much higher number of activated T cells when either AML cell contents or WT-1 peptide was used as the antigen, compared with mice that received the activating biomolecules via a traditional vaccine injection or a “blank” scaffold without any biomolecules. They then “challenged” the mice by injecting them with WT-1-expressing AML cells to mimic the initial onset of the disease. The mice that received either the traditional vaccine or a blank scaffold succumbed to the disease within 60 days, while those that received the cryogel vaccine survived. The survivors were then re-challenged with a second dose of AML cells after 100 days and displayed no signs of disease, demonstrating that the vaccine successfully protected them against recurrence. “The promising outcomes of the combination of this vaccine with chemotherapy may translate to human vaccines that can be personalized yet offer off-the-shelf convenience.” — David Mooney
Share:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to email this to a friend (Opens in new window) Max PixelJAMESTOWN – The Jamestown Board of Public Utilities has renewed its water agreement with the Towns of North Harmony and Busti.As part of the agreement, the BPU agrees to perform the normal operation, maintenance and repair of the existing water distribution mains located within the Town of North Harmony.The cost of any improvements or extensions of the water system in the Town, including replacement of damaged or deteriorated lines, shall be the responsibility of the Town of North Harmony.In the agreement, the Town of North Harmony pledges to pay transportation charges to the Town of Busti and the Village of Lakewood whose lines transport water to the Town of North Harmony. The contract includes agreements of revenue sharing, should new industrial or commercial development occur in the Town of North Harmony, requiring water to be provided by the BPU.The ten-year agreement extends through 2030 and replaces a 2005 contract that had expired in 2019.The new pact does not include an automatic renewal clause but stipulates that negotiations for a 2030 agreement must begin in the ninth year of the contract.
— North Carolina State has administered 1,360 tests for COVID-19 to athletes, coaches and athletic staff with just eight people testing positive. The update came Friday with the school saying that out of the last 765 tests administered since it last released results, only one person has come up positive for the coronavirus. PGA-WYNDHAM CHAMPIONSHIPHoge remains tied for Wyndham lead halfway through roundGREENSBORO, N.C. (AP) — Tom Hoge (HOH’-gee) was still tied with two others for the lead halfway through the second round of the Wyndham Championship on Friday. Hoge was part of a three-way tie with Roger Sloan and Harold Varner III at 8-under par after the first round of the weather-impacted tournament. Hoge shot 68 in the second round to move to 10-under and was tied with Si Woo Kim and Talor Gooch. Kim and Gooch both shot 65s to move atop the leaderboard. The three were a shot in front of British Open champion Shane Lowry and Harris English. Lowry shot a 63 and English a 67. Sloan remained at 8-under after a 70. Varner is part of the afternoon starters. Bamba was diagnosed with COVID-19 on June 11. The 22-year-old appeared in 62 games with the Magic this season but logged only 11 minutes of action in Orlando’s first two seeding games at Walt Disney World. He did not appear in any of Orlando’s final six seeding games.The 7-foot Bamba averaged 5.4 points and 4.9 rebounds for the Magic this season. He was the No. 6 overall pick in the 2018 draft. Orlando plays Milwaukee in the first round of the NBA playoffs.In other NBA news:—Miami Heat forward Derrick Jones Jr. was carted off the court and fitted for a neck brace after colliding with Indiana Pacers center Goga Bitadze late in the third quarter of their game. Jones lay on his stomach for several minutes with his right hand over the back of his head. He had a towel over his face as he was carted off the court. Update on the latest sports August 14, 2020 Associated Press In other Friday action:Andre Burakovsky scored late in the third period, Philipp Grubauer stopped 30 shots and the Colorado Avalanche beat the Arizona Coyotes 3-2 to take a 2-0 lead in their Stanley Cup playoff series. The Coyotes were far more aggressive in Game 2 after being tentative against Colorado’s offensive firepower to in the opener. Game 3 in the best-of-seven series is Saturday in the Edmonton bubble.MLB-METS-DEGROMMets scratch deGrom because of neck tightnessPHILADELPHIA (AP) — The New York Mets have scratched two-time NL Cy Young Award winner Jacob deGrom from his start against the Phillies on Friday. —The Chicago Bulls have fired coach Jim Boylen after the team missed the playoffs again. The Bulls were 22-43 and were one of the eight teams that didn’t qualify for the NBA’s restart at Walt Disney World. That meant they wouldn’t make the postseason for the fourth time in five years. Boylen finished 39-84 as Bulls coach. NHL-PLAYOFFS-CANADIENS-FLYERSTatar, Kotkaniemi scores twice, Canadiens rout Flyers 5-0TORONTO (AP) — Tomas Tatar and Jesperi Kotkaniemi each scored twice, Carey Price stopped 30 shots and the Montreal Canadiens rebounded without coach Claude Julien to rout the Philadelphia Flyers 5-0 on Friday and tie the series at a game apiece. Julien was home in Montreal a day after a stent was placed in a coronary artery. The team said doctors expect a full recovery. Julien was rushed to St. Michael’s Hospital in Toronto overnight Wednesday with chest pain. He had surgery Thursday. Kirk Muller will serve as interim head coach for the rest of the Eastern Conference quarterfinal series. Game 3 is Sunday night. VIRUS OUTBREAK-BASKETBALL HALL OF FAMEBasketball Hall induction moved and delayed to ’21UNDATED (AP) — Kobe Bryant and the rest of this year’s Naismith Memorial Basketball Hall of Fame class won’t be inducted in 2020 — or at the birthplace of basketball. The Hall announced Friday that the enshrinement ceremony will be held May 13-15, 2021, and the entire festivities will be moved to Mohegan Sun Casino in Connecticut.This year was to be a highlight for the Hall of Fame, located in Springfield, Massachusetts. Bryant, killed in January in a helicopter crash, headlined a decorated class featuring Tim Duncan and Kevin Garnett that would have been enshrined in the recently renovated museum. But the coronavirus pandemic scuttled those plans and hit the Hall so hard that it eliminated several full-time positions and cut senior management pay in the 25-40% range.VIRUS OUTBREAK-COLLEGE SPORTS 5 NFL officials take a leave of absence for 2020 seasonUNDATED (AP) — The NFL’s longest-serving on-field official is among five who have opted to take a leave of absence for the 2020 season. Line judge Jeff Bergman, who was entering his 29th year of service, headlined the list released Friday by the NFL.Also in the group is back judge Steve Freeman, who was entering his 20th year. Freeman is a former NFL player who spent 12 of his 13 seasons with the Bills. His son, Brad, is a back judge is entering his seventh season. Also opting out are field judges Greg Gautreaux and Joe Larrew and back judge Tony Steratore.The league said additional officials will be hired and announced.Officials are allowed to opt out under the protocols negotiated by the NFL and NFL Referees Association (NFLRA) because of the coronavirus pandemic.In other NFL news: DeGrom says he has neck tightness, but “everything is fine structurally” and he doesn’t plan to go on the injury list. The right-hander felt soreness playing catch after his last start. He threw from the mound Thursday and thought he could still pitch the opener of a three-game series in Philadelphia but will skip the outing as a precaution. DeGrom is 2-0 with a 2.45 ERA in four starts this season. In other MLB news:—The Cleveland Indians activated pitchers Zach Plesac and Mike Clevinger from the restricted list and optioned them to the team’s alternate training site. The starters had been placed on the restricted list for violating Major League Baseball protocols related to the coronavirus pandemic. Chris Antonetti, Cleveland’s president of baseball operations, said both players drove to Detroit and met with the teammates in an “open forum.” —Oft-injured Yankees star Aaron Judge was placed on the injured list with a right calf strain before Friday night’s game against Boston and manager Aaron Boone is optimistic the outfielder will not miss significant time. The move was retroactive to Wednesday and Boone described the strain as mild after an MRI revealed the injured. NFL-NEWS Denver has lost three straight but is the No. 3 seed in the Western Conference. Toronto is the No. 2 in the Eastern Conference after winning seven of its eight games played in the NBA’s bubble in Central Florida. Denver’s PJ Dozier highlighted his team-high 20-point performance by hitting five of six 3-point shots.NBA-MAGIC-BAMBA OUTMagic say Mo Bamba out for year; center had COVID-19 in JuneLAKE BUENA VISTA, Fla. (AP) — Mo Bamba will not play for the Orlando Magic in this season’s playoffs, after the team announced Friday that he has left the bubble for testing related to his previous bout with coronavirus. Charleston Southern suspends 2020 footballUNDATED (AP) — Charleston Southern is suspending its 2020 football season. The school is part of the Division I Big South Conference and competes in the Football Championship Subdivision. The school said Friday the environment with COVID-19 was too “uncertain” to go forward in the fall, and the decision will let the football team prepare for games in the spring. The Big South and the NCAA have canceled plans for a fall championship, although the league did let member institutions play non-conference games if they wanted in the fall.In other pandemic-related sports news:— The ASUN Conference says it is postponing all fall sports. The nine-team league, formally known as the Atlantic Sun Conference, operates mostly in the Southeast and does not play football. Friday’s announcement from the ASUN’s Presidents’ Council says that providing a spring season for men’s and women’s cross country, men’s and women’s soccer and volleyball is a priority. League schools may continue with such activities like training and practice in accordance with NCAA, local and state guidelines. — Marshall and East Carolina have moved their football game from Aug. 29 to Sept. 12. Both teams had Sept. 12 as an open date after earlier opponents changed their schedules. Marshall was supposed to host Atlantic Coast Conference opponent Pittsburgh that day while East Carolina was traveling to play South Carolina of the Southeastern Conference. The game will be held at East Carolina’s Dowdy-Ficklen Stadium. No time for the game has been determined. — Browns starting center JC Tretter underwent a surgical procedure on his knee and could be out for an extended period. First-year coach Kevin Stefanski didn’t provide many details. Tretter is also the NFLPA president and has been heavily involved in talks over the past few months between the union and NFL to get training camps ready during the COVID-19 pandemic.— The Las Vegas Raiders have taken edge rusher Maxx Crosby off the reserve/COVID-19 list. Crosby was placed on the list last week. He was removed on Friday and took part in his first practice. The list was created for players who either test positive for COVID-19 or have been in close contact with an infected person.— The Atlanta Falcons have re-signed tight end Luke Stocker. He appeared in 15 games for the Falcons last season, including eight starts. Stocker had eight catches for 53 yards. The 32-year-old Stocker spent six seasons with Tampa Bay and two with Tennessee before signing with the Falcons before the 2019 season.— Denzel Mims might have to wait a little while before catching passes from Sam Darnold again. The rookie wide receiver was sidelined at practice Friday with a hamstring injury that could keep him out at least a few days. Mims, the team’s second-round pick in April, was hurt earlier this week while running routes during drills. —The Dallas Cowboys are holding training camp in the Texas heat because the pandemic kept them from traveling to cooler California. It’s the first Cowboys camp to be held entirely in the Dallas area. It’s also the first for new coach Mike McCarthy. He was fired midseason in Green Bay two years ago and was out of the game in 2019. McCarthy is replacing Jason Garrett. Share This StoryFacebookTwitteremailPrintLinkedinRedditNBA-SCHEDULEJohnson scores 23 points to help Raptors top Nuggets 117-109LAKE BUENA VISTA, Fla. (AP) — Stanley Johnson scored 19 of his 23 points in the second half and the Toronto Raptors closed out their regular season with a 117-109 victory over the slipping Denver Nuggets. Both teams entered the game already locked into playoff positions.