The investigational cancer vaccines evaluated in the preclinical study contain antigenic sequences of PRAME and PD-L1 intended to induce anti-cancer immune responses. PRAME is a cancer antigen highly expressed in many different types of cancers and has been associated with different oncogenic processes. PD-L1 represents one of the most important immune checkpoint antigens highly expressed on cancer cells to limit T-cell activation in the tumour microenvironment.
"CK Life Sciences has a growing pipeline of cancer vaccines in various stages of development. The preclinical efficacy results of our dual-targeting PRAME/ PD-L1 cancer vaccines in liver cancer are promising and we hope to start clinical trials in the coming years," said Melvin Toh, Vice President & Chief Scientific Officer at CK Life Sciences. "Liver cancer is the second most common cause of cancer death in Asia and remains a major unmet medical need. We plan to investigate the PRAME/ PD-L1 dual-targeting cancer vaccines further in liver cancer and other cancer types known to over-express PRAME and PD-L1."
DETAILS ON POSTER PRESENTATION:
- Abstract 1336: Cancer vaccine co-targeting PRAME and PD-L1 exerts significant tumour growth inhibition in syngeneic mouse hepatocellular carcinoma models
- Authors: Kin-Tak Chan, Chen-Yi Chiang, Chai Ho, Melvin Toh, Hsin-Wei Chen
- Session Date and Time: Saturday, November 4th from 9:00 a.m. - 8:30 p.m. Pacific Standard Time
In this preclinical study, we investigated whether dual-antigen cancer vaccines co-targeting PRAME and PD-L1 could suppress tumour growth in both prophylactic and therapeutic syngeneic mouse hepatocellular carcinoma (HCC) models.
Two recombinant fusion protein vaccines comprised of PD-L1 and PRAME with or without GM-CSF were synthesised and formulated with a Toll-like receptor 9 agonist CpG oligodeoxynucleotide and aluminum hydroxide for vaccination. In the prophylactic tumour model study, the vaccines were administrated subcutaneously twice at a two-week interval before implantation of mouse HCC cells expressing PRAME, followed by weekly vaccination. In the therapeutic model study, the vaccines were administrated weekly into the animals after tumour cell implantation. Body weight and tumour volume were measured three times a week.
All mice experienced a recoverable body weight loss without any abnormal behavior or reduction of activity after vaccination. In the prophylactic model (n=10 mice), both fusion protein vaccines significantly inhibited tumour growth, with 76.4% (P) and 59.5% (P) tumour growth inhibition (TGI) compared to control group, respectively. Importantly, there were some vaccinated mice without palpable tumour mass at the end of the study. These results were consistent with that found in the therapeutic model study (n = 10 mice), in which both vaccines significantly inhibited tumour growth, with 43.4% (P) and 40.7% (P) TGI, respectively, and prolonged animal survival compared to the control group (P.
The results of this preclinical study clearly highlight the potential of simultaneously targeting PRAME and PD-L1 by fusion protein vaccination in cancer immunotherapy.
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REFERENCES
[1] Gradecki S, Slingluff C, Gru A. J Cutan Pathol. PRAME expression in 155 cases of metastatic melanoma.
Accessed at https://onlinelibrary.wiley.com/doi/10.1111/cup.13876.
[2] Oyama K, Kanki K, Shimizu H, Kono Y, Azumi J, Toriguchi K, Hatano E, Shiota G. Gastrointest Tumors. Impact of preferentially expressed antigen of melanoma on the prognosis of hepatocellular carcinoma.
Accessed at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465675/.
[3] Thongprasert S, Yang PC, Lee J, Soo R, Gruselle O, Myo A, Louahed J, Lehmann F, Brichard V, Coche T. Lung Cancer. The prevalence of expression of MAGE-A3 and PRAME tumor antigens in East and South East Asian non-small cell lung cancer patients.
Accessed at https://pubmed.ncbi.nlm.nih.gov/27794402/.
[4] Epping M, Hart A, Glas A, Krijgsman O, Bernards R. Br J Cancer. PRAME expression and clinical outcome of breast cancer.
Accessed at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527791/.
[5] Ahmad S, Borch T, Hansen M, Andersen M. Cancer Immunol Immunother. PD-L1-specific T cells.
Accessed at https://pubmed.ncbi.nlm.nih.gov/26724936/.
Hashtag: #CKLifeSciences #CancerVaccines #R&D
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CK Life Sciences Int'l., (Holdings) Inc.
CK Life Sciences Int'l., (Holdings) Inc. (stock code: 0775) is listed on the Stock Exchange of Hong Kong. Bearing the mission of improving the quality of life, CK Life Sciences is engaged in the business of research and development, manufacturing, commercialisation, marketing, sale of, and investment in, products and assets which fall into three core categories - nutraceuticals, pharmaceuticals and agriculture-related. CK Life Sciences is a member of the CK Hutchison Group. For additional information, please visit www.ck-lifesciences.com.
About PRAME
PRAME is a protein commonly expressed by cancer cells, including melanoma (1), liver cancer (2), lung cancer (3) and breast cancer (4). PRAME contributes to the development and spread of cancer cells, and studies have shown that high levels of PRAME are associated with poor outcomes in cancer patients (2,4). In recent years, researchers have been exploring ways to target PRAME using immunotherapy, such as T-cell therapy and cancer vaccines, as a potential treatment for cancer.
About PD-L1
PD-L1 is a protein expressed by certain immune cells and cancer cells. It plays a role in suppressing anti-cancer immune responses by binding to a receptor called programmed death-1 (PD-1) on T-cells, limiting the activation of T-cells, thereby helping cancer cells evade the immune system. Antibodies that can block the interaction of PD-L1 and PD-1 have been approved for the treatment of certain types of cancer. Recent studies have shown the presence of PD-L1-specific T-cells in both healthy individuals and cancer patients, which suggests that targeting PD-L1 with T-cell therapy or cancer vaccines could be a promising approach for cancer treatment (5).
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