Injectable Hydrogel Scaffolds Were Used For T Cell Expansion In Tumors

Immunotherapy is a treatment that uses the body’s own immune system to treat malignant tumors.Adoptive immunotherapy strategies effectively increase the number of specific T cells in cancer patients by injecting isolated autologous tumor-specific T cells,amplified the tumor-specific T cells in vitro after adequate stimulation,and thereby elicit a powerful anti-tumor response.However,in the process of T cell amplification,the existing technical means have some defects: the return T cells to the tumor site efficiency is low in vitro amplification and reinfusion.Due to the immunosuppressive microenvironment of the tumor site,there are problems such as depletion of T cells arriving at the tumor site,etc;In vivo amplification strategy,the low efficiency of antigen presenting cells targetting lymphatic organs results in low amplification efficiency.Meanwhile,because of antigen presenting cell surface protein structure,it is easy to be cleared in vivo,low activity,short cycle length.The systemic distribution of cells will cause systemic toxic and side effects.Therefore,in this study,the artificial antigen presenting cells were fixed in situ in the tumor by hydrogel,and the infiltrating T cells in the tumor were amplified to realize the direct growth of T cells in the tumor site and bypass the defects of adoptive cell metastasis.The main research contents are as follows:The thermo-sensitive hydrogel PCGA-PEG-PCGA triblock copolymer was prepared by using polyethylene glycol 1500,ethylene lactide and ε-caprolactone as raw materials.The average molecular weight of PCGA-PEG-PCGA triblock copolymer was 10065.The prepared hydrogel copolymer powder was prepared into a hydrogel solution with mass fraction(wt %)of 28,and the hydrogel solution could realize the phase transition from liquid sol state to solid gel state at the temperature of 37 ℃.At the same time,the hydrogel solution with this mass fraction has a higher hardness after being transformed into a gel,which can meet the needs of drug fixation as a carrier.Artificial antigen presenting cells based on mesoporous silica microspheres(MSMS)were successfully prepared.Three kinds of stimulus signals were modified onto mesoporous silica microspheres(MSMS)particles,in which stimulus signal 1 and stimulus signal 2 were modified on the surface of the particles by streptavidin,showing good stability.Stimulus signal 3(IL-2)was encapsulated inside the liposome and released in the form of paracrine.The release curve showed that the release process was mainly concentrated in the first 4 days and gradually stabilized on the 10 th day.The amplification times of the artificial antigen presenting cells to the primary CD3 T cells in mice were positively correlated with the number of artificial antigen presenting cells,and the maximum amplification times was 4 times.The combination of hydrogel and artificial antigen presenting cells had a certain amplification effect on the infiltrating T cells in the tumor,and the amplification ratio of CD3 T cells was about twice.Meanwhile,the proportion of CD8 T cell subsets in CD3 T cells increased significantly,and there was a phenomenon of clustering.These results suggest that this strategy can bypass adoptive cell metastasis and avoid some drawbacks of current adoptive immunotherapy by directly expanding tumor-infiltrating T cells.