Induced tumor associated autoantibodies (iTAAs) by hapten plus drugs for targeting oncogenic nuclear antigens at sentinel lymph node of pancreatic cancer

Lei Wang, Baofa Yu, Jian Zhang, Yan Han, Guoqin Zheng

Article ID: 8925
Vol 8, Issue 2, 2024

VIEWS - 39 (Abstract) 13 (PDF)

Abstract


Background: the abscopal is a hypothesis of effect on non-irradiated tumors after localized radiation therapy which associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs). When TAAs interact with hapten within tumor after hapten plus chemotherapy drugs intratumoral injection to pancreatic cancer like tumor lysates vaccine, TAAs-hapten stimulates the immune system as a neu antigen and produces autologous tumor antibodies, it is called induced tumor-associated autoantibodies (iTAAs) which is lightly difference to aTAAs since epitope of antigen linked with hapten. Method: immunofluorescence (IF) was applied for detect the binding of the iTAAs in tumor cells at sentinel lymph node. Results: aTAAS naturally could not target and bind the TAAs in tumor since due to immune tolerance. The iTAAs can target and bind the TAAS, also the iTAAs targeted in the tumors of sentinel lymph node with complements C help, it was found Cmyc (P = 0.0017 at one week; P = 0.0001 at two weeks), p53 (P = 0.0373; 29.13 ± 6.91, and P = 0.0254), and Zeta (P = 0.1513, P = 0.0044) increased significantly in the tumor cells or perinuclear tumor cells in lymph node at one and two weeks after treatment. Conversely, IMP1 (P = 0.6154; P = 0.0138), Koc (P = 0.5684, P = 0.0103), Survivn (P = 0.1020; P = 0.0147) and Rala (P = 0.3226; P = 0.0249) increased significantly in the cell or perinuclear of tumor in lymph node at two weeks later following. Conclusions: it indicated all of iTAAs plays a function in the binding of original cellular tumor genes at sentinel lymph node while the aTAAs could not bind the cellular tumor genes at lymph node due to immune tolerance. We could make a hypothesis: TAAs inside the cancer cells’ nuclei can be targeted by the iTAAs which produced by hapten enhanced intratumoral chemotherapy. The iTAA may play a distinctive role in controlling tumor cell growth and resulting in an abscopal effect, which is one of hapten associated with TAA induced immune response.


Keywords


tumor associate antigen (TAA); tumor-associated autoantibodies (TAA) induced autologous tumor antibodies (iATA); neu antigens; hapten; hapten induced immunotherapy

Full Text:

PDF


References


1. Janeway CA, Travers P, Walport M, et al. The Humoral Immune Response. Garland Science. 2001.

2. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology. 2012; 23: viii6-viii9. doi: 10.1093/annonc/mds256

3. Soman AD, Collins JM, DePetris G, et al. Isolated supraclavicular lymph node metastasis in pancreatic adenocarcinoma: a report of three cases and review of the literature. JOP. 2010; 11(6).

4. Heo CK, Bahk YY, Cho EW. Tumor-associated autoantibodies as diagnostic and prognostic biomarkers. BMB Reports. 2012; 45(12): 677–685. doi: 10.5483/bmbrep.2012.45.12.236

5. Sun G, Ye H, Wang X, et al. Autoantibodies against tumor-associated antigens combined with microRNAs in detecting esophageal squamous cell carcinoma. Cancer Medicine. 2019; 9(3): 1173–1182. doi: 10.1002/cam4.2792

6. Dudas SP, Chatterjee M, Tainsky MA. Usage of cancer associated autoantibodies in the detection of disease. Cancer Biomarkers. 2010; 6(5–6): 257–270. doi: 10.3233/cbm-2009-0138

7. Yu B, Han Y, Fu Q, et al. Awaken Immune Cells by Hapten Enhanced Intratumoral Chemotherapy with Penicillin Prolong Pancreatic Cancer Survival. Journal of Cancer. 2023; 14(8): 1282–1292. doi: 10.7150/jca.82985

8. Yu B, Zhang J, Fu Q, et al. Successful targeting in situ of an oncogenic nuclear antigen by hapten induced tumor associated autoantibodies (iTAA). Scientific Reports. 2023; 13(1). doi: 10.1038/s41598-023-36757-2

9. Gross BP, Wongrakpanich A, Francis MB, et al. A Therapeutic Microparticle-Based Tumor Lysate Vaccine Reduces Spontaneous Metastases in Murine Breast Cancer. The AAPS Journal. 2014; 16(6): 1194–1203. doi: 10.1208/s12248-014-9662-z

10. Diao L, Liu M. Rethinking Antigen Source: Cancer Vaccines Based on Whole Tumor Cell/tissue Lysate or Whole Tumor Cell. Advanced Science. 2023; 10(22): e2300121. doi: 10.1002/advs.202300121

11. Schnurr M, Galambos P, Scholz C, et al. Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: an in vitro model for the assessment of tumor vaccines. Cancer Res. 2001; 61(17): 6445–6450.

12. Lau SP, Klaase L, Vink M, et al. Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study. European Journal of Cancer. 2022; 169: 20–31. doi: 10.1016/j.ejca.2022.03.015

13. Dai L, Ren P, Liu M, et al. Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma. Clinical Immunology. 2014; 152(1-2): 127-139. doi: 10.1016/j.clim.2014.03.007

14. Tang ZM, Ling ZG, Wang CM, et al. Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis. Plos One. 2017; 12(7): e0182117. doi: 10.1371/journal.pone.0182117

15. Yu BF, Lu Y, Gao F, et al. Hapten-enhanced therapeutic effect in advanced stages of lung cancer by ultra-minimum incision personalized intratumoral chemoimmunotherapy therapy. Lung Cancer: Targets and Therapy. Published online January 2015: 1–11. doi: 10.2147/lctt.s70679

16. Kaminski JM, Shinohara E, Summers JB, et al. The controversial abscopal effect. Cancer Treatment Reviews. 2005; 31(3): 159–172. doi: 10.1016/j.ctrv.2005.03.004

17. Dai L, Peng XX, Tan EM, et al. Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma. Oncotarget. 2016; 7(13): 16985-16995. doi: 10.18632/oncotarget.7707

18. Im K, Mareninov S, Diaz MFP, et al. An Introduction to Performing Immunofluorescence Staining. Methods Mol. Biol. 2019: 299–311. doi: 10.1007/978-1-4939-8935-5

19. Yu BF., Chen D., Zhang J, et al. An Acute Inflammation with Special Expression of CD11 & CD4 Produces Abscopal Effect by Intramoral Injection Chemotherapy Drug with Hapten in Animal Model. Journal of Immunological Sciences. 2022; 6(3): 1-9. doi: 10.29245/2578-3009/2022/3.1236




DOI: https://doi.org/10.24294/ti.v8.i2.8925

Refbacks

  • There are currently no refbacks.


Copyright (c) 2024 Lei Wang, Baofa Yu, Jian Zhang, Yan Han, Guoqin Zheng

License URL: https://creativecommons.org/licenses/by/4.0/

This site is licensed under a Creative Commons Attribution 4.0 International License.