Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations

Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy

“…These results suggest that CD8 + T cells are involved in the eradication of PHEO tumors during MBTA therapy, but CD4 + T cells are important for the long-term memory after MBTA therapy of murine PHEO. Similarly, previous results from MBTA therapy of murine pancreatic adenocarcinoma (Panc02) have shown that CD4 + T cells are important for the complete eradication of tumor growth and resistance to its recurrence in CD8 −/− knockout mice, suggesting that CD4 + T cells might play diverse anti-tumor roles in different types of murine tumor models [37]. During the assessment of T cells in bilateral PHEO tumors, only CD8 + T cells and their subpopulation of CD8 E/EM T cells were elevated in both tumors directly after the first MBTA injection cycle, suggesting a faster acute response in tumors compared to CD4 + T cells.…”

“…Despite the potential of this therapy to systematically change the tumor microenvironment into immunologically "hot," reduce tumor growth, and prolong the survival of treated animals, we could not achieve the complete eradication of murine PHEO tumors with high tumor burden. Our previous study demonstrated that only simultaneous MBTA therapeutic injections into both tumors could potentially treat the bilateral Panc02 model [37]. Therefore, an optimal therapeutic approach, along with MBTA therapy, to increase the antitumor effect in metastatic murine PHEO tumors, is yet to be investigated.…”

Intratumoral immunotherapy of murine pheochromocytoma shows no age-dependent differences in its efficacy

“…Such results are consistent with our previous results with young mice bearing pheochromocytoma, pancreatic adenocarcinoma, melanoma, or colon carcinoma where MTBA immunotherapy was efficient in 62-83% ( 14 – 16 ). Similarly, the previous studies of the efficacy of MBTA in pancreatic adenocarcinoma, Panc02 tumor model ( 15 , 17 ), were done in young animals only while pancreatic cancer most often affects older adults ( 40 ). Our results of MBTA in bilateral Panc02 tumor model, which was tested in 8-weeks and 72-weeks old mice, representing 15 years and 57 years in human, showed the similar reduction of tumors and prolonged survival of treated mice as published before ( 17 ).…”

“…Similarly, the previous studies of the efficacy of MBTA in pancreatic adenocarcinoma, Panc02 tumor model ( 15 , 17 ), were done in young animals only while pancreatic cancer most often affects older adults ( 40 ). Our results of MBTA in bilateral Panc02 tumor model, which was tested in 8-weeks and 72-weeks old mice, representing 15 years and 57 years in human, showed the similar reduction of tumors and prolonged survival of treated mice as published before ( 17 ). Such results suggest that MBTA therapy is effective even in this hard-to-treat Panc02 model with two advanced tumors without any age differences.…”

“…MBTA therapy has been previously tested in various subcutaneous tumor models in mice, such as melanoma (B16-F10), pancreatic adenocarcinoma (Panc02), colon carcinoma (CT26), and pheochromocytoma (PHEO, MTT cells) with the complete elimination of tumors in 62-83% of mice depending on tumor type ( 14 – 16 ). MBTA therapy has also shown systemic immune response in PHEO models including its metastatic model, bilateral Panc02, and bilateral CT26 model, where the therapy resulted in slower progression of non-treated distal tumors and significant prolongation of survival of treated mice ( 14 , 16 , 17 ). Moreover, strong infiltration of both adaptive and innate immune cells was observed in treated and distal tumors in case of bilateral PHEO model ( 18 ).…”