Could Adding a TLR9 Agonist Improve Responses in Metastatic Melanoma?

Excerpt:

“A phase I trial found promising activity and good tolerability with the combination of pembrolizumab and a stimulant of Toll-like receptor 9 (TLR9) known as SD-101 in patients with unresectable or metastatic melanoma, particularly in those who had not received prior anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy.

“PD-1/PD-L1 inhibition has improved outcomes in metastatic melanoma, and studies have indicated that combination therapy can increase immune responses further. “Despite the improvement in response rates with combination immunotherapy, a large unmet need remains,” wrote study authors led by Antoni Ribas, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center.”

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TLR9 Agonist CMP-001-Pembrolizumab Combination Shows Early Efficacy for Metastatic Melanoma Resistant to Anti-PD-1

Excerpt:

A combination of CMP-001, an intratumoral Toll-like receptor 9 (TLR9) agonist, and pembrolizumab (Keytruda), tested in patients with metastatic melanoma resistant to PD-1 checkpoint inhibition, was well tolerated and had clinical activity according to preliminary data presented from the ongoing phase Ib clinical trial at the AACR Annual Meeting 2018, April 14-18, in Chicago.

” ‘Checkpoint inhibition is quickly becoming a key tool for oncologists to treat cancer,’ said Mohammed Milhem, MBBS, clinical professor of internal medicine at the University of Iowa, Iowa City. ‘However, there are many  that either initially respond to checkpoint inhibition and then progress, or never respond to this therapy to begin with. Finding safe and effective therapies for these patients is critical.’ ”

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Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”