Establishment of P38Bf, a Core-Fucose-Deficient Mouse-Canine Chimeric Antibody Against Dog Podoplanin.

In this study, we developed and produced several mouse-canine chimeric antibodies originating from PMab-38. A mouse-canine chimeric antibody of subclass A (P38A) and a mouse-canine chimeric antibody of subclass B (P38B) were transiently produced using ExpiCHO-S cells. Core-fucose-deficient P38B (P38Bf) was developed using FUT8 knockout ExpiCHO-S cells. We compared the binding affinities, antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) of P38A, P38B, and P38Bf against Chinese hamster ovary (CHO)/dPDPN cells. Flow cytometry analysis showed that the KD of P38A, P38B, and P38Bf were 1.9 × 10-7, 5.2 × 10-9, and 6.5 × 10-9, respectively. Both P38B and P38Bf revealed high ADCC activities against CHO/dPDPN cells; P38Bf demonstrated significantly higher ADCC compared with P38B, especially at low concentrations. P38B and P38Bf exhibited higher CDC activities against CHO/dPDPN cells. Conversely, P38A did not exhibit any ADCC or CDC activity. In summary, P38Bf is a good candidate for antibody therapy against dPDPN-expressing canine cancers. PMID: 30362926 [PubMed - in process]
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research

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ConclusionsThe updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes.Patient summaryIn the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other pre...
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionsThe persistent complete response after third-line treatment for relapsed chemotherapy-resistant cervical cancer presented in this case highlights the potential of immunotherapy for patients with advanced cervical cancer impressively.To our knowledge, this is the first report of an isolated immune-related vulvitis under nivolumab. This adverse event might be underdiagnosed and mistreated, however, it is of importance due to its impact on quality of life, sexual wellbeing and compliance of patients. Successful IRAE management may enable prolonged immune checkpoint inhibitor therapy. In the future, routine molecula...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsWe discover prominent and distinct associations between TIBs antibody isotypes and survival in lung adenocarcinoma carrying specific driver mutations. These findings indicate that particular types of tumor-immunity relations could be beneficial in particular driver mutation context, which should be taken into account in developing strategies of cancer immunotherapy and combination therapies. Specificity of protective B cell populations in specific cancer subgroups could become a clue to efficient targeted immunotherapies for appropriate cohorts of patients.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Together, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T cell clones within a progressing tumor, and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas. PMID: 31645352 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionTregs exert suppressive effects on NKT cell tumoricidal function by inducing more CD4− NKT cell anergy and less CD4+ NKT cell anergy. Both Treg depletion and NKT cell recovery from the anergy state may be important for improving the clinical efficacy of NKT cell-based immunotherapy in patients with advanced cancers.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
CONCLUSION: The results of the Keynote-048 study have already led to the approval of pembrolizumab in the first line for platin-sensitive HNSCC in the USA and the expected approval in Europe will presumably change the therapeutic landscape in the long term. In the future, effective therapies for patients without a response to programmed cell death 1 (PD-1)/PD-L1 inhibition will be needed. PMID: 31612261 [PubMed - as supplied by publisher]
Source: HNO - Category: ENT & OMF Tags: HNO Source Type: research
ConclusionsOur results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8+ T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8+ T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8+ T cells in the tumor microenvironment.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Abstract Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course ...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
We describe a case of digital ulcerative lichenoid dermatitis resembling ulcerative cutaneous lichen planus that occurred during pembrolizumab therapy for oral squamous cell carcinoma. The patient developed a painful ulcer on his index finger 18 months into therapy. Biopsy revealed epidermal ulceration with intense lichenoid dermatitis. Immunohistochemical study revealed intense CD8 positivity at the ulcer's edges and marked CD163 positivity at its base. Although idiopathic forms of this type of lichenoid dermatitis...
Source: Dermatology Online Journal - Category: Dermatology Source Type: research
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