The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma

Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20–30% of neoantigens predicted in silico to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4+. Therefore, it warrants further exploration to enhance neoantigen-specific CD8+ T cells responses. Since neoantigens are naturally weak antigens, we asked whether foreign T help epitopes could enhance their immunogenicity. In present study, we chose 4 weak B16F10 neoantigens as vaccine targets, and fused them to the transmembrane domain of diphtheria toxin, namely DTT-neoAg. Strikingly, the vaccine elicited anti-tumor CD8+ T cells responses and enhanced tumor infiltration of both T cells and NK cells. Impressively, DTT-neoAg vaccine significantly deterred tumor growth with the inhibition rate reached 88% in the preventive model and 100% in the therapeutic model at low dose of tumor challenge. Furthermore, after second challenge with higher dose of tumor cells, 33.3% of the immunized mice remained tumor-free for 6 months in the therapeutic model. Because DTT is a non-toxic domain of diphtheria toxin, it may be not of great concern in terms of safety as a Th epitope provider. Thus, the fusion strategy employed by this study ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Authors: Montazeri K, Bellmunt J Abstract Introduction: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or metastatic UC (mUC) with FGFR3 or FGFR2 alterations, accounting for 15-20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.Areas covered: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presen...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
Authors: Jakubowska K, Koda M, Kisielewski W, Kańczuga-Koda L, Famulski W Abstract The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
The objective of the present study was to evaluate the beneficial effect of endorectal power Doppler/grayscale ultrasound-guided biopsy over that of mpMRI/TRUS-guided biopsy for decision-making regarding prostatectomy in males with a high risk of prostate cancer. Data regarding endorectal power Doppler/grayscale ultrasound-guided biopsies and mpMRI/TRUS-guided biopsies of 1,094 males with elevated specific prostate antigen, were included. Radical prostatectomy was performed in males aged
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Toma M, Beluşică L, Stavarachi M, Apostol P, Spandole S, Radu I, Cimponeriu D Abstract Colorectal cancer (CRC) is a disease preventable in up to 50% of the patients by lifestyle modifications. The preventive strategy for the decrease in the incidence and mortality of CRC is based on understanding the relations between the environmental and genetic factors. The most important identified risk factors for CRC are aging, personal and familial history of CRC or adenomas, hereditary colon cancer syndromes, dietary patterns, and inflammatory bowel disease. The purpose of this review is to update data referring ...
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Conclusions: CD200 has a great impact in diagnosing B- chronic lymphoproliferative disorders, especially when we want to determine the origin of a CD19, CD5 positive population and distinguish between CLL and MCL. CD 23 is a reliable marker in those cases, but, as we showed, CD23 might have a lower specificity than CD200 for CLL. We added CD200 in our panels in order to diagnose chronic lymphoproliferative disorders, not to replace CD 23, but to improve and save time in our diagnostic process. The high expression of CD200 in CLL and HCL could open the option for new- targeted therapy (anti-CD200). PMID: 31803290 [PubMed]
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Publication date: 1 January 2020Source: Colloids and Surfaces B: Biointerfaces, Volume 185Author(s): L. Vallan, J. Hernández-Ferrer, L. Grasa, J.M. González-Domínguez, M.T. Martínez, B. Ballesteros, E.P. Urriolabeitia, A. Ansón-Casaos, A.M. Benito, W.K. MaserAbstractGiven the potential applications of fluorescent carbon nanoparticles in biomedicine, the relationship between their chemical structure, optical properties and biocompatibility has to be investigated in detail. In this work, different types of fluorescent carbon nanoparticles are synthesized by acid treatment, sonochemical trea...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Conclusion: Several health maintenance aspects are inadequately addressed by GIs and PCPs, in part because of conflicting perceptions of responsibility. Clear guidelines and better GI/PCP communication are required to ensure effective health maintenance for patients with IBD. PMID: 31528131 [PubMed]
Source: Ochsner Journal - Category: General Medicine Tags: Ochsner J Source Type: research
Conclusion and Perspective With in-depth understandings of antibodies, linkers, and payloads, ADCs have also achieved great development. The linkage strategy and target diversity have already improved the delivery of the payloads to tumor tissues and reduced exposure to normal tissues. With the development of payloads, some novel potent payloads are used by ADCs, which allows researchers to exploit novel linkers to attach the antibody and payloads without disturbing their potency (Dragovich et al., 2018). Furthermore, some irrelevant antigen-target ADCs also may exert toxicity to tumor cells due to the vascular gap of tum...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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