A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+  tumors in hPD-1 transgenic mouse model and contributes immune memory formation

ConclusionA novel HER2-targeting ADC combined with immune checkpoint inhibitors can achieve remarkable effects in mice and elicit long-lasting immune protection in a hHER2+  murine breast cancer model. This study provides insights into the efficacy of RC48 therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research

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World J Clin Oncol. 2021 Oct 24;12(10):868-881. doi: 10.5306/wjco.v12.i10.868.ABSTRACTEndometrial cancer is the most common gynecological cancer in developed countries, and its incidence has increased. The majority of patients with endometrial cancer have an early disease and favorable prognosis; however, a significant proportion of endometrial cancer, which mainly comprises high-grade or type II endometrial cancer such as serous, clear cell, and carcinosarcoma, shows advanced/recurrent disease and dismal prognosis. Novel therapeutic development is required for patients with aggressive endometrial cancers. Recent genomic a...
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Source Type: research
A recent clinical trial showed prolonged progression-free survival in human epidermal growth factor receptor 2 (HER2)-positive advanced stage and recurrent endometrial serous carcinomas when trastuzumab was added to traditional chemotherapy. Approximately one third of these tumors are HER2-positive and have been described to show unique characteristics of HER2 protein expression and gene amplification, including significant intratumoral heterogeneity, in recent studies. However, currently, there are no standard protocols for the selection of optimal specimen type or algorithm for HER2 testing in endometrial serous carcinom...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE CORPUS: Original Articles Source Type: research
Conditions:   Non-small Cell Lung Cancer (NSCLC);   Human Epidermal Growth Factor Receptor 2 (HER2) Negative Breast Cancer;   Ovarian Cancer;   Cervical Cancer;   Endometrial Cancer;   Esophageal Cancer;   Gastric Cancer and Gastroesophageal Junction (GEJ) Carcinoma;   Colorectal Cancer;   Ex ocrine Pancreatic Adenocarcinoma;   Appendiceal Adenocarcinoma;   Pseudomyxoma Peritonei Intervention:   Drug: SGN-STNV Sponsor:   Seagen Inc. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Pesantez Maria Vidal Barbara Adamo Montserrat Muñoz Patricia Galván Laura Barberá Miriam Cuatrecasas Mathias Christgen Hans Kreipe Inés Monge-Escartín Patricia Villagrasa Dolors Soy Tommaso Giarratano Maria Vittoria Dieci Pierfranco Conte Nadia Harbeck Valentina Guarneri Aleix Prat Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that t...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
288Objectives: We have reported CRs and cures using anti-HER2/anti-DOTA hapten bispecific pretargeted radioimmunotherapy (anti-HER2-DOTA-PRIT) approach for treatment of HER2-expressing breast cancer using beta- or alpha-emitting isotopes. As part of this work, we documented identical pharmacodynamics of the theranostic pairs: In-111- versus Ac-225 - radiohapten chelates (proteus DOTA, PrDOTA; Mol Imaging Biol 2019 21: 167-335). Herein we report on an extension of our studies to a second HER2-expressing solid tumor using a NCI-N87 gastric cancer mouse model. Methods: Initial biodistribution (using In-111) and therapy studie...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Oncology & amp; Translational II Source Type: research
Abstract NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch s...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the ren...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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