Abstract 5584: PHY906(YIV-906), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Immune checkpoint blockade therapy: anti-PDL1, anti-PD1, anti-PD1/CTLA4 against melanoma
Authors: Lam Wing , jiang Zaoli , han Xue , Liu Shwu-Huey , Chen Lieping , Cheng YungChi 
Published: July 2017

Abstract
Immune checkpoint blockade therapy has recently been recognized as a breakthrough in cancer treatment. Currently the FDA has approved Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD1) and Nivolumab (anti-PD1), and Atezolizumab (anti-PDL1) for the treatment of several types of cancers, including melanoma. However, colitis and diarrhea are commonly found in these immunotherapies, particularly in anti-PD1/CTLA4 therapy. PHY906(YIV-906) is inspired by the Huang Qin Tang, which was first described in Chinese texts 1800 years ago for the treatment of numerous gastrointestinal symptoms. Consistent preparations of PHY906 could be manufactured apart 10 years. In animal studies, PHY906 can increase the anti-tumor activity of a broad spectrum of chemotherapies while promoting damaged intestinal tissue recovery via mutliple targets. Several clinical results suggest that PHY906 had potential to increase the therapeutic index of cancer treatments (chemotherapy, radiation) by prolonging life and improving patient quality of life. We hypothesize that PHY906 can reduce diarrhea caused by anti-PD-L1, anti-PD1, and/or in combination with CTL4 without compromising their anti-tumor activity. We studied the effect of PHY906 in combination with anti-PDL1, anti-PD1, anti-CTLA4 and anti-PD1/CTLA4, using subcutaneously implanted B16F10 melanoma in Black B16 mice. Results indicated that PHY906 enhanced the anti-tumor activity of anti-PD1, anti-PDL1, or anti-PD1/CTLA4; but not anti-CTLA4 alone, in vivo. In addition, PHY906 did not compromise the action of anti-PD-L1 in brain implanted B16 tumor. PHY906 in combination with all of the antibodies had no impact of body weight change or different type of blood cells counts. PHY906 reduced mRNA expression of several inflammation markers, including TNFa, MCP1, ICAM, IL2, in ileum or colon tissues following anti-PD1 or anti-CTLA4 treatment. In cell culture, PHY906 was found to have modulation effect on Indoleamine 2,3-dioxygenase (IDO) which is a key resistance factor to immune checkpoint blockade therapies. Overall, PHY906 can increase the therapeutic index for anti-PDL1, antiPD1, or anti-PD1/CTLA4 in against melanoma. We are planning to initiate a clincal trial to determine if PHY906 could enhance the therapeutic index of anti-PD1/CTLA4 for the treatment fo melanoma in patient. This work was supported by grant (1PO1CA154295-01A1) from National Cancer Institute (NCI), NIH, USA. Dr. Yung-Chi Cheng is a fellow of National Foundation for Cancer Research (NFCR), USA.
Citation Format: Wing Lam, Zaoli jiang, Xue han, Shwu-Huey Liu, Lieping Chen, YungChi Cheng. PHY906(YIV-906), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Immune checkpoint blockade therapy: anti-PDL1, anti-PD1, anti-PD1/CTLA4 against melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5584. doi:10.1158/1538-7445.AM2017-5584