Tag: Montaner

Dr. Luis J. Montaner and lab find common, persistent symptoms for long-haulers by reviewing a multitude of research studies.

An international team of researchers led by The Wistar Institute’s lead scientist on HIV-cure research has published a review that codifies some of the key take-aways from a sample size of 2,833 patients with long COVID.

Led by Wistar’s Dr. Luis J. Montaner, director of the HIV-1 Immunopathogenesis Laboratory and leader of the HIV Research Program within the Vaccine & Immunotherapy Center, and published in the Journal of Leukocyte Biology, the review offers supporting evidence that RS-CoV-2 (PASC), or long COVID, reflects tissue injuries to a patient’s system that underscores the vulnerabilities of individuals with the disease or the immunological consequence of their system responding to COVID.

“We conducted a review of all the available literature, summarizing what criteria we could define as long COVID that unifies patients across studies. We then took those unifying themes that identify commonalities in long COVID and identified targets for research we could potentially do something about,” Montaner said. “If you search long COVID, there are multiple different presentations, multiple different organ systems, and it is a challenge to come up with unifying principles of what disease process results in long COVID. We focused on identifying common principles of immunological disturbance and tissue injury mechanisms that could be supported by studies of long COVID to date.”

Many Wistar researchers are using machine learning to crunch complex data. That wasn’t the case here.

“It was more a more manual, elbow grease method,” Montaner said. “Each study used different definitions and data points but with similar populations. We listed all the studies, all the patients, all the definitions used, and the criteria we used to coalesce them. That is something that machines cannot do.”

Montaner was surprised to identify distinct patterns on how long COVID may affect the outcome of either acute injury or the long and projected injury to tissues.

They found mechanisms that contribute to symptoms such as inflammation, antigens that persist even after initial infection and microbial translocation (also known as leaky gut) all contribute to long COVID and can be affected by things like age and gender.

“Long COVID presents itself in many ways so it’s important to understand biologically what causes each type of symptom,” Montaner said. We also hope to address the ongoing debate between treating early against the virus versus treating the immune system against tissue injury caused by our own immune response. Our work will advance efforts to identify therapy strategies to avoid tissue injury leading to long COVID from that initial infection.”

This was not the first time a Wistar-led team has taken this roadmap approach.

“When COVID arrived in 2020, one of the first things we did was conduct a comprehensive review of all the reports that provided insight on the immunological modulation within the disease itself, highlighting what we knew and what was available,” Montaner said.

The objective now is to advance research again but on long COVID, noting that the prior 2020 review has been cited by world researchers more than 500 times since publication.

Wistar received a $4M grant from the State of Pennsylvania in 2021 to advance COVID research on vulnerable populations, in part because the organization has gained access to vulnerable populations through its work with patients living with HIV or people with substance use disorder in Center City Philadelphia, Kensington and other areas associated with drug use.

Luis J. Montaner, D.V.M., D.Phil, and his team are making tremendous strides studying the ability of natural killer (NK) cells, a type of immune cell, to wipe out HIV-infected cells. Meanwhile, other groups within Wistar’s HIV Research Program, which Montaner leads, are in hot pursuit of alternative immunotherapy strategies, such as modified antibodies and CAR T cell therapies, to stamp out infected cells.

The research progress of all these labs was recently pole-vaulted forward thanks to a generous and visionary seven-figure unrestricted planned estate gift from Robert A. Fox (Bob). Bob, who passed away in 2021, helped transform Wistar into a leading biomedical research institute, through numerous donations that he and his wife, Penny, made and his two-decade role on Wistar’s Board of Trustees.

The new unrestricted gift enabled the purchase of three state-of-the-science advanced instrumentation and equipment. Flow cytometry is technology that isolates specific types of cells from tissue samples for analysis, along with a host of other customizable features, that will benefit and advance a wide range of Wistar scientists. Another is a technology platform consisting of two pieces of equipment for high-resolution imaging and spatial profiling of cellular structures and molecules at unprecedented speed and scale. The system will forge new insights into interactions between cancer and immune cells and the tumor microenvironment that nearly every lab at Wistar can deploy. The third is equipment, which is dedicated to the HIV Research Program, for a live cell analysis system that tracks cells growing in tissue culture plates.

“The investment is going to accelerate an excellence that is already here,” says Montaner, who is the vice president of Scientific Operations and associate director for Shared Resources at Wistar. “It is not a bet by any means. It is a sure thing that, by providing these tools, scientists can answer questions we couldn’t before, and answer the questions we were after better with added insights that will allow to move novel concepts towards clinical trials faster,” he explains.

The live cell analysis system will allow all laboratories in the Wistar HIV program to pinpoint exactly how well and how quickly various immunotherapy strategies are killing HIV-infected cells. The equipment also opens the door to being able to gather multiple timepoints on samples from HIV-infected patients, which are typically of very limited quantity.

The equipment is now bolstering research on developing combination immunotherapy as a cure for HIV for which the Montaner Lab and other groups in the BEAT-HIV Martin Delaney Collaboratory were awarded a five-year, $29.15M award from the NIH last year.

One of the most powerful aspects of an unrestricted gift is the time it saves. The traditional route that Wistar, and research institutes in general, take to obtain new, cutting-edge equipment is to apply for an NIH Shared Instrumentation Grant. But applications are only accepted once a year, and if grants are reviewed well and awarded, which has been the case for many of Wistar’s last submissions, it still takes one to two years to receive the equipment. Instead, an unrestricted gift entrusts Wistar to direct the support where it thinks it can have the greatest benefit and purchase equipment immediately.

“Unrestricted gifts allow Wistar scientists the capacity to quickly seize opportunities to remain competitive in an environment that is very dynamic when it comes to platforms that allow you to innovate,” Montaner says. “This gift advances what we are doing right away, while simultaneously increasing our competitive edge to grow our programs by writing new grant proposals that take advantage of the state-of-the-art capacities.”

In addition to the work in the HIV Research Program to help bring immunotherapies to the clinic, the investment will benefit Wistar’s research on cancer therapies and COVID-19 vaccines. “The impact is immediate with both present and future returns for all of these programs,” Montaner says.

This year, The Wistar Institute hosted the Annual Jonathan Lax Memorial Award Lecture virtually, bringing together HIV scientists and activists on a global stage. Celebrating 26 years of continuous HIV research collaboration, the event was streamed on June 28, 2022, and saw attendees from North and South America, Europe, Africa, and Asia. The event opened with a music video by Moses “Supercharger” Nsubuga, HIV Outreach and HIV Cure Research Advocate and musician from Uganda and the Stigmaless Band performing their song “Optimistic”. It set a positive and engaging tone, reminding everyone that researchers and activists are working toward a common goal of HIV cures that prevent, control, and treat the virus.

The keynote speaker delivering the Lax Lecture was Mike McCune, M.D., Ph.D., head of the HIV Frontiers Initiative of the Bill & Melinda Gates Foundation, who emphasized the scientific progress toward curative interventions for HIV for all parts of the world. He highlighted efforts toward the development of gene therapies and “single shot” vaccine candidates and looking forward to clinical trials.

McCune expanded on his view of the ideal HIV cure. It would be available in an outpatient clinic; it would be given in one shot—like a vaccine—and durable for three years, yet a lifetime would be ideal; it must prevent or control infection but doesn’t require complete eradication; and it would be affordable for underdeveloped nations/low-income nations at $1000-2000 per administration. Also, McCune mentioned creating an affordable home testing kit, similar to COVID-19 test kits, for people to monitor if the disease is under control.

McCune shared, “We need to have a long-term vision and we need to have steps along the way that show we’re moving towards it.”

The event also hosted a panel centered around the question “What does an HIV cure mean to you?”. The global community discussion included Moses “Supercharger” from Uganda; Philister Adhiambo, Community Liaison Officer and HIV Cure Advocate from Kenya; and Michael Louella, Community Engagement Project Manager of the defeatHIV collaborative in the U.S. They all agreed that research can move forward if it prioritizes the community. Their strong perpectives came from the realities they see every day in their communities: participation in cure-directed studies, of being female with HIV/AIDS, living with HIV/AIDS in low- and middle-income countries outside the U.S., remaining on antiretrovirals for decades not knowing the toll it takes on their bodies, and stigmatized people that lost opportunities because they were HIV positive.

“26 years ago, we set out to make a difference in HIV/AIDS treatment strategies through the most cutting-edge research, done shoulder-to-shoulder with clinicians, advocates, and people living with HIV/AIDS in Philadelphia,” said Luis J. Montaner, D.V.M., D.Phil., Herbert Kean, M.D., Family Professor, leader of the HIV Research Program at The Wistar Institute, and co-principal investigator of the BEAT-HIV Delaney Collaboratory. “Our program has now grown beyond the region and country to gain a network across the globe. Our mission hasn’t changed, but we have grown into a global center to report the most groundbreaking HIV cure research together with community input.”

McCune stated, “Now is the time to move forward. Solving these challenges is not going to happen overnight, but it’s starting now.”

Dr. Luis Montaner is a transformative leader in HIV research. Throughout his tenure at Wistar, his discoveries to find an HIV cure have elevated both the prestige and scientific prowess of the Institute while most importantly, helped inform the treatments for people around the globe suffering from HIV.

Montaner has spent the last 26 years at The Wistar Institute researching HIV infection and how to boost the immune system to fight the disease. With the goal of advancing treatment strategies toward HIV eradication, his research combines virology and immunology to study the mechanisms of HIV virus infection. Montaner is also involved in overseeing patient enrollment into innovative clinical trials through advocacy partners such as Philadelphia FIGHT, and this summer, he and his partners were awarded a $29.15 million Martin Delaney Collaboratories for HIV Cure Research award to the BEAT-HIV Martin Delaney Collaboratory to advance combination immunotherapy research towards a cure for HIV. This funding extends a grant originally awarded in 2016 based on research progress to date.

Dr. Luis Montaner joined Wistar in 1995 as an assistant professor and was promoted to professor in 2007. He holds many positions at Wistar including vice president, Scientific Operations; Hebert Kean, M.D., Family Professor; associate director for Shared Resources, The Wistar Institute Cancer Center; and director, HIV-1 Immunopathogenesis Laboratory and leader, HIV Research Program. Since his arrival, Luis has been a proponent of the power of scientific collaboration. He believes that by joining intellectual and resource strengths with partners, he can advance research faster and achieve better outcomes. As illustrated in the map, the Montaner lab collaborative studies extend from Philadelphia across the United States and Puerto Rico to Mexico, Europe, South America, Southern Africa, and Asia.

His work relies on laboratory models of viral infection, such as animal models, together with clinical cohort studies, to provide a clinic-to-bench research program. This approach informs new strategies to combat HIV that may also change how we think about prevention and treatment of other infectious diseases and cancer.

“Research moves faster and with greater impact when you bring together several experts with different knowledge and areas of discovery,” said Dr. Montaner. “Just like an orchestra conductor can draw different sounds to support the execution of a symphony, the ability to draw from basic researchers, animal model experts, clinicians, industry experts, international advisors, and community members under a common shared effort helps us accelerate progress towards an HIV cure.”

Nothing exemplifies the power of collaboration more than the incredible progress the HIV research field has enabled over the last forty years in diagnosing, treating, and preventing HIV. Even recently, from 2010 to 2017, the rate of HIV-related deaths among people 13 years and older in the United States fell by nearly half according to a study from the Center for Disease Control and Prevention.

Much has been accomplished in the HIV research field, however there is still so much more to do, including the continued pursuit of a successful HIV vaccine and ultimately a cure for HIV. In this pursuit for a cure, Dr. Montaner currently leads one of the largest coalitions of NIH-funded, HIV cure-directed research under the BEAT-HIV Delaney Collaboratory. This enormous consortium brings together more than 70 top HIV researchers from academic research institutions around the world working with government, nonprofit organizations, and industry partners to test combinations of several novel immunotherapies under new preclinical research and clinical trials. The common goal of the Collaboratory is to achieve an accessible and safe strategy that can either sustain control of HIV without the continued use of current therapies and/or eradicate HIV.

While global collaborations are important, Luis has always been a huge proponent of the power of local collaborations. Within Philadelphia, his lab has a long-standing partnership with Philadelphia FIGHT, a comprehensive health services organization providing primary care, consumer education, research and advocacy for people living with HIV/AIDS and those at high risk. Representing an academic-community partnership that is unique in HIV research, Philadelphia FIGHT and the University of Pennsylvania along with the Robert I. Jacobs Fund of The Philadelphia Foundation, developed the HIV-1 Patient Partnership Program to provide clinical material for basic research and to sponsor the Jonathan Lax Memorial Lecture. Research with clinical material obtained from this Program is focused on mechanisms of AIDS immunopathology. This collaborative link between Montaner’s research team and more than 5,000 people living with HIV/AIDS in the Philadelphia region has led to the largest HIV Cure clinical trial to date — the BEAT-HIV Study. Their partnership with Philadelphia FIGHT strives to develop trusted relationships and maintain meaningful, bi-directional lines of communication between scientists and communities most affected by HIV. HIV Social Science has been a recent addition to the Montaner lab program to enhance both their preclinical and community engagement efforts.

Opportunity for progress is unique and unparalleled at present but so is Wistar’s collective responsibility to deliver.