Biomaterial-delivered one-two punch boosts netbet casino promo code immunotherapy

Integrated biomaterials approach that enhances adoptively transferred T cell therapy with netbet casino promo code vaccine technology provides strong and long-lasting effects against solid tumors

By Benjamin Boettner, Wyss netbet casino promo code for Biologically Inspired Engineering | Press contact

July 13, 2023

An image of the netbet casino promo code-permeable porous structure of an injectable SIVET immuno-material — The researchers visualized the netbet casino promo code-permeable porous structure of an injectable SIVET immuno-material using scanning electron microscopy analysis (SEM). Credit: Wyss Institute at Harvard University

netbet casino promo code immunotherapy has brought major improvement in patient survival and quality of life, especially with the success of adoptive T cell and immune checkpoint inhibitor therapies. Unfortunately, in contrast to different blood cancers, the effectiveness of adoptive T cell therapies in the treatment of solid tumors, which comprise about 90% of all tumors, has been very limited because of several formidable barriers.

In adoptive T cell therapies, a patient’s T netbet casino promo code with cytotoxic potential are engineered outside the body so that they can bind specific features (antigens) on the surface of tumor netbet casino promo code, which converts them into tumor-killing netbet casino promo code. However, after being reinfused into the donor patient’s blood circulation, they have to travel long distances to reach a solid tumor with only a fraction of them ever arriving there. On-site, they need to infiltrate the often difficult-to-penetrate tumor mass, while their cytotoxic activity is suppressed by tumor netbet casino promo code and their surrounding tissue microenvironment. In addition, the further solid tumors grow, the more heterogenous their cell composition becomes, which also includes tumor netbet casino promo code’ repertoire of surface antigens, and thus allows them to “escape” the attack of adoptively transferred T netbet casino promo code.

Now, a team of netbet casino promo code-engineers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss netbet casino promo code for Biologically Inspired Engineering at Harvard University have developed a novel biomaterials-based immunotherapy netbet casino promo code named SIVET (short for “synergistic in situ vaccination enhanced T cell”) that has the potential to break down these barriers. The injectable netbet casino promo code enables both the local delivery of antigen-specific adoptively transferred T cells directly to tumor sites and their prolonged activation, as well as a broader engagement of the host immune system to provide much longer-lasting anti-tumor effects against tumor cells carrying new antigens. Validated in mice carrying melanomas, a particularly aggressive type of solid tumor, SIVET enabled the fast shrinking of tumors and long-term protection against them. The findings are published in Nature Communications.

“In the SIVET approach, we essentially combined fast-acting adoptive T cell therapy with long-term protective netbet casino promo code vaccine technology in a locally delivered integrated biomaterial. Advancing this approach towards patient settings could help addresses several limitations of current immunotherapies and offers new inroads into the treatment of solid tumors,” said senior author David NetBet live casino, the Robert P. Pinkas Family Professor of Bioengineering at SEAS and a Founding Core Faculty member at the Wyss netbet casino promo code.

netbet casino promo code convergences

In extensive previous work, Mooney’s team had pioneered netbet casino promo code-based netbet casino promo code vaccines that are able to program key immune-orchestrating dendritic netbet casino promo code, known as antigen-presenting netbet casino promo code (APCs), into tumor-fighting netbet casino promo code in vivo. Despite the netbet casino promo code vaccines being able to provide broad therapeutic and prophylactic benefits, their tumor-directed effects take time to manifest in the body. On the other hand, patient-specific adoptively transferred T cells are ready-made to attack tumor cells upon first contact but produce rather short-lived responses.

“Our new platform fully leverages our expertise with adoptive T cell and netbet casino promo code vaccine technologies. Combining the best of these two worlds in a multi-pronged biomaterial-based approach allows the fast debulking of existing tumor masses while engaging the immune system on a much deeper level through the localized delivery, concentration, and activation of diverse tumor-fighting immune cells,” said co-first author Kwasi netbet casino promo code, who completed his Ph.D. in Mooney’s lab and is currently a Translational Immunotherapy Scientist at the Wyss netbet casino promo code.

Adu-Berchie, Mooney, and the team developed a cryogel netbet casino promo code that contains collagen and alginate polymers cross-linked into a 3-dimensional porous scaffold. While the alginate provides the netbet casino promo code with structural support, collagen serves to provide ligands needed for T cell trafficking. Following injection of the engineered T cell depot close to a tumor site, the compressed netbet casino promo code recovers its original shape and starts releasing the cytokine interleukin 2 (IL2) to facilitate the expansion of the delivered T cells, which move out of the netbet casino promo code and onto the tumor to carry out an attack.

T netbet casino promo code stained with different immunofluorescence reagents — After injection and taking action against a solid tumor, SIVETs recruit and further activate a variety of T netbet casino promo code that are stained with different immunofluorescence reagents in this image. Credit: Wyss Institute at Harvard University

In addition, the netbet casino promo code releases a second cytokine, abbreviated as GMCSF, which attracts host APCs into the porous scaffold that then also become concentrated and activated with the help of an adjuvant molecule known as CpG close to the tumor. The activated APCs also infiltrate the tumor mass where they take up new antigens created by dying tumor cells that disintegrate as a result of the T cell attack. The APCs then migrate to nearby lymph nodes where they orchestrate a broader vaccine response by presenting processed antigens to other immune cell types, including other cytotoxic T cells that attack the tumor in consecutive waves, as well as memory T cells that stand by for future tumor recurrences.

The researchers investigated SIVET in a mouse model carrying melanoma tumors and found that the multi-functional netbet casino promo code enabled better control over the tumors than the same adoptively transferred T cells injected directly into the tumor site or infused into the blood stream of the animals. SIVETs enabled the delivered T cells to remain active longer and minimized the exhaustion of all T cells in the tumor microenvironment when compared to control conditions.

“Through their vaccine component, SIVETs trained the immune system to reject melanoma tumors for significantly prolonged periods of time, and thus allowed the animals to survive for significantly longer than animals that received any of our control treatments. This likely was facilitated by the netbet casino promo code’s ability to prevent the growth of tumor cells that escape the attack of adoptively transferred T cells due to their loss of the initially targeted antigen,” said Adu-Berchie. “Identifying a tumor-specific antigen against which potent donor-specific T cells can be generated for adoptive transfer could provide SIVETs with enough to go on to initiate a tumor attack on a much broader front and scale.”

The study is also authored by other past and present members of Mooney’s group, including Joshua Brockman, Yutong Liu, Tania To, David Zhang, Alexander Najibi, Yoav Binenbaum, Alexander Stafford, Nikolaus Dimitrakakis, Miguel Sobral, and Maxence Dellacherie. It was supported by grants from the National Institutes of Health (award #U54 CA244726 and #U01 CA214369), National Science Foundation (award #MRSEC DMR-1420570), and Food and Drug Administration (award #R01 FD006589), as well as the National netbet casino promo code Institute (award #5K00CA234959).

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Biomaterial-delivered one-two punch boosts netbet casino promo code immunotherapy

Integrated biomaterials approach that enhances adoptively transferred T cell therapy with netbet casino promo code vaccine technology provides strong and long-lasting effects against solid tumors

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Biomaterial-delivered one-two punch boosts netbet casino promo code immunotherapy

Integrated biomaterials approach that enhances adoptively transferred T cell therapy with netbet casino promo code vaccine technology provides strong and long-lasting effects against solid tumors

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