Periodic Reporting for period 1 - CD28 (Probing CD28 as checkpoint for T cell co-stimulation in cancer and infection)
Okres sprawozdawczy: 2021-10-29 do 2023-10-28
Regarding aim 2, the therapeutic potential of the anti-PD-1-sialidase conjugates to reestablish CD28 co-stimulation was evaluated making use of suitable murine models of tumor and chronic infection. Firstly, the sialidase-anti-PD-1 conjugates were prepared and the protocol optimized to get enough amounts for the corresponding in vitro and in vivo tests with exhausted T cells. The sialidase and anti-PD-1 were independently expressed and then chemically coupled using a sortase-based strategy. As a result, a homogeneous product consisting of a dimeric anti-PD-1 with two attached sialidases was isolated and its sialidase activity confirmed in vitro (Work package 4 completed). Then, the in vitro tests with exhausted T cells extracted from hosts were performed. Finally, the in vivo tests were done to compare the efficiency of anti-PD-1-sialidase conjugates with that of anti-PD-1 alone in the reduction of solid tumors. As no convincing differences were found at this point between both treatments, further scheduled studies were discontinued and the whole strategy rethought. At this point, all tasks of work package 3 were considered as done, but the experiments didn’t yield the expected results.