MSGID: 1:317/3 64b0cf8c   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Biomaterial-delivered one-two punch boosts cancer immunotherapy    
      
     Date:   
         July 13, 2023   
     Source:   
         Wyss Institute for Biologically Inspired Engineering at Harvard   
     Summary:   
         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. Now immune-engineers have developed a   
         novel biomaterials-based immunotherapy approach named SIVET that   
         has the potential to break down these barriers. The injectable   
         biomaterial 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.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
      
   ==========================================================================   
   FULL STORY   
   ==========================================================================   
   Cancer 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 cells with cytotoxic potential   
   are engineered outside the body so that they can bind specific features   
   (antigens) on the surface of tumor cells, which converts them into   
   tumor-killing cells.   
      
   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 cells and their surrounding tissue   
   microenvironment. In addition, the further solid tumors grow, the more   
   heterogenous their cell composition becomes, which also includes tumor   
   cells' repertoire of surface antigens, and thus allows them to "escape"   
   the attack of adoptively transferred T cells.   
      
   Now, a team of immune-engineers at the Wyss Institute for Biologically   
   Inspired Engineering at Harvard University and Harvard John A. Paulson   
   School of Engineering and Applied Sciences (SEAS) have developed a   
   novel biomaterials- based immunotherapy approach named SIVET (short for   
   "synergistic in situ vaccination enhanced T cell") that has the potential   
   to break down these barriers. The injectable biomaterial 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 cancer 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 Mooney, Ph.D., who is a Founding   
   Core Faculty member at the Wyss Institute and the Robert P. Pinkas Family   
   Professor of Bioengineering at SEAS.   
      
   Mooney leads the Wyss Institute's Immunomaterials Platform and   
   co-leads the NIH-funded Immuno-Engineering to Improve Immunotherapy   
   (i3) Centercoordinated at the Wyss Institute and focused on creating   
   biomaterials-driven approaches to enable anti-cancer immunotherapy in   
   solid tumor settings.   
      
   Biomaterial convergences In extensive previous work, Mooney's team had   
   pioneered biomaterial-based cancer vaccines that are able to program key   
   immune-orchestrating dendritic cells, known as antigen-presenting cells   
   (APCs), into tumor-fighting cells in vivo. Despite the cancer 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   
   cancer 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   
   Adu-Berchie, Ph.D., who completed his Ph.D.   
      
   in Mooney's lab and is currently a Translational Immunotherapy Scientist   
   at the Wyss Institute.   
      
   Adu-Berchie, Mooney, and the team developed a cryogel biomaterial that   
   contains collagen and alginate polymers cross-linked into a 3-dimensional   
   porous scaffold. While the alginate provides the biomaterial 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 biomaterial 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 biomaterial   
   and onto the tumor to carry out an attack.   
      
   In addition, the biomaterial 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 biomaterial 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 biomaterial'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.   
      
   "This study is a beautiful convergence of two powerful immunotherapy   
   approaches that are programmed in the body to synergize with each   
   other. This work once again demonstrates the power of taking an   
   unconventional trans-disciplinary approach -- in this case, combining   
   strategies from materials science and tissue engineering with immunology   
   -- to create novel and more powerful therapeutics for the eradication of   
   solid cancers," said Wyss Founding Director Donald Ingber, M.D., Ph.D.,   
   who is also the Judah Folkman Professor of Vascular Biology at Harvard   
   Medical School and Boston Children's Hospital, and the Hansjo"rg Wyss   
   Professor of Bioinspired Engineering at SEAS.   
      
   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 Cancer Institute (award #5K00CA234959).   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Brain_Tumor # Cancer # Lung_Cancer # Immune_System #   
                   Lymphoma # Skin_Cancer # Colon_Cancer # Ovarian_Cancer   
       * RELATED_TERMS   
             o Monoclonal_antibody_therapy o Cancer o T_cell o Brain_tumor   
             o Immune_system o Tumor_suppressor_gene o Natural_killer_cell   
             o BRCA1   
      
   ==========================================================================   
      
    Print   
      
    Email   
      
    Share   
   ==========================================================================   
   ****** 1 ****** ***** 2 ***** **** 3 ****   
   *** 4 *** ** 5 ** Breaking this hour   
   ==========================================================================   
       * Overflowing_Cosmic_'Jug' * Ghost_Stars_in_Our_Galaxy *   
       Multiple_Ecosystems_in_Hot_Water * How_an_'AI-Tocracy'_Emerges   
       * Building_a_Better_Tree_With_CRISPR_Gene_Editing *   
       Unprecedented_Control_Of_Every_Finger_of_...   
      
       * Widespread_Death_of_Insects:_Air_Pollution   
       * Webb_Celebrates_First_Year_of_Science *   
       New_Parkinson's_Disease_Cell_Therapies *   
       Circular_DNA_Grabs_DNA_Repair_Mechanism:_...   
      
      
   Trending Topics this week   
   ==========================================================================   
   HEALTH_&_MEDICINE Brain_Tumor Nervous_System Stem_Cells MIND_&_BRAIN   
   Intelligence Behavior Brain_Injury LIVING_&_WELL Behavior Healthy_Aging   
   Child_Development   
      
      
   ==========================================================================   
      
   Strange & Offbeat   
   ==========================================================================   
   HEALTH_&_MEDICINE   
   Surgical_and_Engineering_Innovations_Enable_Unprecedented_Control_Over_Every   
   Finger_of_a_Bionic_Hand   
   Capturing_the_Immense_Potential_of_Microscopic_DNA_for_Data_Storage   
   Revolutionary_Self-Sensing_Electric_Artificial_Muscles MIND_&_BRAIN   
   The_Sound_of_Silence?_Researchers_Demonstrate_People_Hear_It   
   AI_Tests_Into_Top_1%_for_Original_Creative_Thinking   
   Everyone's_Brain_Has_a_Pain_Fingerprint_--_New_Research_Has_Revealed_for_the   
   First_Time LIVING_&_WELL   
   These_Lollipops_Could_'Sweeten'_Diagnostic_Testing_for_Kids_and_Adults_Alike   
   Grocery_Store_Carts_Set_to_Help_Diagnose_Common_Heart_Rhythm_Disorder_and   
   Prevent_Stroke Illusions_Are_in_the_Eye,_Not_the_Mind   
   Story Source: Materials provided   
   by Wyss_Institute_for_Biologically_Inspired_Engineering_at   
   Harvard. Original written by Benjamin Boettner. Note: Content may be   
   edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Kwasi Adu-Berchie, Joshua M. Brockman, Yutong Liu, Tania W. To,   
      David K.   
      
         Y. Zhang, Alexander J. Najibi, Yoav Binenbaum, Alexander Stafford,   
         Nikolaos Dimitrakakis, Miguel C. Sobral, Maxence O. Dellacherie,   
         David J.   
      
         Mooney. Adoptive T cell transfer and host antigen-presenting cell   
         recruitment with cryogel scaffolds promotes long-term protection   
         against solid tumors. Nature Communications, 2023; 14 (1) DOI:   
         10.1038/s41467- 023-39330-7   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230713142018.htm   
      
   --- up 1 year, 19 weeks, 3 days, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 218/700 226/30 227/114   
   SEEN-BY: 229/110 112 113 307 317 400 426 428 470 664 700 291/111 292/854   
   SEEN-BY: 298/25 305/3 317/3 320/219 396/45 5075/35   
   PATH: 317/3 229/426