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1414 Antitumor effect of HER2-hICD vaccine combining with HER2 ADC depending on T cell existence in a mouse model: pooled analysis
  1. JinHo Kang1,
  2. Hyo-Hyun Park1,
  3. Jee Hyun Choi1,
  4. Jinback Lim1,
  5. Hye-Ran Kim2,
  6. Seong-Yong Jang3,
  7. Min-Ah Kim3,
  8. Myeong-Kyu Park3,
  9. Yun-Hee Park4,
  10. Soyeon Lim4,
  11. Chul-Woong Chung4,
  12. Jin Kyeong Choi5,
  13. Eunkyo Joung1 and
  14. Hun Jung1
  1. 1Aston Sci. Inc., Seoul, Republic of Korea
  2. 2Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
  3. 3Korea Testing and Research Institute, Hwasun, Republic of Korea
  4. 4LegoChem Biosciences, Inc., Daejeon, Republic of Korea
  5. 5Jeonbuk National University Medical School, Jeonju, Republic of Korea


Background AST-301 (pNGVL3-hICD) is a plasmid DNA-based cancer vaccine encoding HER2-ICD that is not only a potent oncogenic protein but also immunogenic antigen in human cancer. The clinical efficacy and safety of AST-301, including long-term immunogenicity and survival, were demonstrated in a HER2-positive breast cancer population in a phase 1 study completed (PN109, NCT00436254). In this study, we did comparison of the antitumor effect of a combination regimen of AST-301 and HER2 ADC in athymic (immunodeficient) and CD34+ humanized models using human gastric cancer cell line.

Methods NCI-N87 cells were mixed with the same amount of matrigel to formulation tumors in mice. CD34+ humanized (n=4/group) and Athymic BALB/c nude (n=7/group) mouse were assigned. When the tumor size were reached to 100–200 mm3, study drug regimen was administrated. AST-301 (100 ug/animal, intradermal injection, mixed with rhuGM-CSF as an immune adjuvant) was immunized once a week to a total of fourth. LCB01 (IV injection) was administered with a single dosing.

Results In CD34+ humanized mouse model, a combination regimen of AST-301 and LCB01 (low does) showed better anti-tumor efficacy than LCB01 (high does) alone (TGI rate at Day 22, 64% vs 39%), and even AST-301 mono-treatment showed better anti-tumor efficacy than LCB01 (low does) alone (TGI rate at Day 22, 32% vs 24%). Whereas, in athymic BALB/c nude mouse model, AST-301 and LCB01 (low does) did not show better anti-tumor efficacy than LCB01 (high does) alone (TGI rate at day 25, 52% vs 69%).

Immune cell changes was profiled by FACS analysis in splenocytes and tumor cells of mice. In the CD34+ humanized mouse model, cytotoxic T cell was relatively increased in tumor site by the combination regimen of AST-301 with LCB01 and LCB01(low does) alone. Also, cytotoxic T cells was increased in splenocyte by AST-301 mono-treatment and LCB01(low does) alone.

Conclusions Given that clear antitumor effect of AST-301-based regimen was observed in CD34+ humanized mouse model than athymic BALB/c nude mouse model, it is proven that the presence of T cells is very crucial in pharmacological efficacy of cancer vaccine approach and relevant in-vivo efficacy study. These translational researches are supporting a clinical study of AST-301 combining with HER2-ADCs.


  1. Disis ML, et al. Safety and Outcomes of a Plasmid DNA Vaccine Encoding the ERBB2 Intracellular Domain in Patients With Advanced-Stage ERBB2-Positive Breast Cancer. JAMA Oncol. 2023;9(1):71–78.

  2. Disis ML, et al. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol. 2009;27(28):4685–4692.

  3. Disis ML, et al. Existent T cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 1994;54:16–20.

Ethics Approval Korea testing & Research institute IRB Approval No. IAC2022–2963, Gwangju Institute of Science and Technology IRB Approval No. GIST-2022–034

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