Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer

Benzon, Benjamin; Glavaris, Stephanie; Simons, Brian W.; Hughes, Robert M.; Ghabili, Kamyar; Mullane, Patrick; Miller, Rebecca M.; Nugent, Katriana; Shinder, Brian; Tosoian, Jeffrey J.; Fuchs, Ephraim J.; Tran, Phuoc T.; Hurley, Paula J.; Vuica‐Ross, Milena; Schaeffer, Edward M.; Drake, Charles G.; Ross, Ashley E.

doi:10.1038/s41391-018-0035-z

Cited by 37 publications

(24 citation statements)

References 35 publications

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“…The development of biology is helpful in finding therapeutic targets for diseases [27]. Biomedicine has made great progress in cancer treatment [28]. Recent studies have shown the success of using inhibitory peptides to disrupt specific protein-protein interactions and their pertinent biological events [29–32].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells

Liang

Zhang

et al. 2019

BMC Cancer

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Background We aimed to develop inhibitory short peptides that can prevent protein interactions of SOS1/EPS8/ABI1 tri-complex, a key component essential for ovarian cancer metastasis. Methods Plasmids containing various regions of HA-tagged ABI1 were co-transfected into ovarian cancer cells with Flag-tagged SOS1 or Myc-tagged EPS8. Co-immunoprecipitation and GST-pulldown assay were used to identify the regions of ABI1 responsible for SOS1 and EPS8 binding. Inhibitory short peptides of these binding regions were synthesized and modified with HIV-TAT sequence. The blocking effects of the peptides on ABI1-SOS1 or ABI1-EPS8 interactions in vitro and in vivo were determined by GST-pulldown assay. The capability of these short peptides in inhibiting invasion and metastasis of ovarian cancer cell was tested by Matrigel invasion assay and peritoneal metastatic colonization assay. Results The formation of endogenous SOS1/EPS8/ABI1 tri-complex was detected in the event of LPA-induced ovarian cancer cell invasion. In the tri-complex, ABI1 acted as a scaffold protein holding together SOS1 and EPS8. The SH3 and poly-proline+PxxDY regions of ABI1 were responsible for SOS1 and EPS8 binding, respectively. Inhibitory short peptides p + p-8 (ppppppppvdyedee) and SH3–3 (ekvvaiydytkdkddelsfmegaii) could block ABI1-SOS1 and ABI1-EPS8 interaction in vitro. TAT-p + p-8 peptide could disrupt ABI1-EPS8 interaction and suppress the invasion and metastasis of ovarian cancer cells in vivo. Conclusions TAT-p + p-8 peptide could efficiently disrupt the ABI1-EPS8 interaction, tri-complex formation, and block the invasion and metastasis of ovarian cancer cells.

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Section: Introductionmentioning

confidence: 99%

Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells

Liang

Zhang

et al. 2019

BMC Cancer

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“…Recently, the effects of combinations of cryotreatment and immune checkpoint inhibitors have been reported [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Co-stimulation of the immune system with tumor antigens via cryosurgery in the presence of a “primed” immune system, pretreated with CTLA-4 and PD-1 combination therapy, would theoretically result in a synergistic effect of local tumor and distant metastasis regression or an abscopal effect [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the effect of a combination of cryotreatment and immunotherapy has been reported [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. In these basic and clinical research, cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1) antagonists play a complementary role in the activation of cancer immunity, and immunotherapy followed by cryosurgery could demonstrate to induce a more cancer-specific immune response to distant lesions.…”

Section: Introductionmentioning

confidence: 99%

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

Yonezawa

Murakami

Demura

et al. 2021

IJMS

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We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

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“…Prostate cancer (PCa) is the most common cancer in males and the second leading cause of cancer death [1,2]. Until now, available therapies for advanced stages of this disease are still limited, and their effectiveness is far from satisfactory.…”

Section: Introductionmentioning

confidence: 99%

Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer

Zhang¹,

Chen²,

Li³

et al. 2020

J. Cancer

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Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways. Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8 + TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa.Key words: programmed death receptor-1, T cell immunoglobulin and mucin domain-containing protein-3, prostate cancer, vaccine, immunotherapy.

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Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer

Cited by 37 publications

References 35 publications

Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells

Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer

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