A New Virtual Reality: Benefits and Barriers to Providing Pediatric Gender-Affirming Health Care Through Telehealth.

Purpose: Access to early, multidisciplinary, gender-affirming health care significantly improves the psychosocial well-being of transgender and gender diverse youth. The Doernbecher Gender Clinic (DGC) is an interdisciplinary pediatric gender clinic consisting of endocrinology, psychology, and social work. Following the initiation of modified operations in March 2020 due to the COVID-19 pandemic, the DGC converted all interdisciplinary new patient appointments to telehealth. The purpose of this article is to (1) describe the model of care implemented during modified operations, (2) compare the number of new patients seen before and after modified operations, and (3) to contextualize this information with data from a patient satisfaction survey. Method: Retrospective chart review was used to determine how many interdisciplinary new patient appointments occurred before and during modified operations. Additional variables included age, gender, visit modality (phone or video), geographic location, and number of caregivers who participated. In addition, patients and families who attended appointments since modified operations were invited to complete a prospective survey regarding their experience and satisfaction with these appointments, and the narrative responses to questions about advantages and disadvantages were analyzed thematically. Results: Chart review revealed a similar number and make up of new patient appointments before and after the initiation of modified operations. The percentage of patients residing in other urban areas outside of the Portland metro increased over the course of the three time periods, but not to a significant degree. Survey results suggest that both telehealth and in-person visits have advantages and disadvantages with regard to (1) access and (2) comfort. Families appear to differ with regard to their priorities in each area. Conclusion: Telehealth has the potential to provide quality pediatric gender-affirming health care without sacrificing the benefits of an interdisciplinary team-based approach.

A phase I clinical study of VB4-845: weekly intratumoral administration of an anti-EpCAM recombinant fusion protein in patients with squamous cell carcinoma of the head and neck.

VB4-845 is a scFv-Pseudomonas exotoxin A fusion construct that targets epithelial cell adhesion molecule (EpCAM). A phase I trial was conducted to determine the maximum tolerated dose (MTD) of VB4-845 when administered as weekly intratumoral (IT) injections to patients with squamous cell carcinoma of the head and neck (SCCHN). Secondary objectives included the evaluation of the safety, tolerability, pharmacokinetic profile, and immunogenicity, and a preliminary assessment of tumor response. Twenty patients with advanced, recurrent SCCHN were treated weekly for four weeks in ascending dose cohorts of 100, 200, 330, 500, 700, and 930 microg. The MTD was established as 930 microg with a dose limiting toxicity of elevated liver enzymes in two of five patients. VB4-845 therapy was well tolerated with common treatment-related adverse events of injection site reactions, fever, gastrointestinal disorders, and elevated liver enzyme levels. All patients developed antibodies to VB4-845 by the end of the study, but only seven patients had neutralizing antibodies. Preliminary efficacy data found 87.5% of EpCAM-positive patients had a positive response to VB4-845 therapy. Noninjected dermal metastases were also resolved in one patient. VB4-845 IT therapy is safe and feasible and warrants further clinical evaluation for the treatment of SCCHN.

A targeted proteomic approach for the identification of tumor-associated membrane antigens using the ProteomeLab PF-2D in tandem with mass spectrometry.

Mapping differential expression of soluble proteins has become fairly routine using chromatofocusing in combination with the reversed-phase HPLC (ProteomeLab PF-2D by Beckman Coulter Inc.); however, identification of membrane antigens has not been reported thus far. In this report, we demonstrate a targeted proteomic approach employing immunoprecipitation, prior to 2D-LC separation, in tandem with MS/MS that can be used to identify tumor-associated membrane antigens. This system is very sensitive and reproducible in that only 1/4th the amount of starting material is required for analysis as compared to gel-based analysis, and permits a focused environment for eliminating non-specific interactions leading to an accurate resolution of the cognate antigen. This system also circumvents the well-known limitations associated with gel-based approaches. This approach has been validated in the identification of ErB2/HER-2 and was subsequently used to identify CD44E as the cognate antigen for VB1-008, one of our fully human, tumor-specific, monoclonal antibodies.

Effective tumor targeting: strategies for the delivery of Armed Antibodies.

It has long been realized that the presence of tumor-associated antigens offers an excellent opportunity for targeted cancer therapy and hence an improved clinical benefit for cancer patients. Advances in the field of antibody engineering as well as the characterization of toxins, such as diphtheria toxin and Pseudomonas exotoxin A, have enabled the routine construction of recombinant immunotoxins, which we have termed Armed Antibodies. The selective toxicity and mechanism of action of these molecules could potentially provide an excellent clinical alternative to conventional anticancer agents which have many unacceptable side effects. Although considerable clinical success has been achieved using immunotoxin therapy, particularly for B-cell malignancies, the treatment of solid tumors remains highly challenging. To successfully treat solid tumors that are not amenable to local therapy, immunotoxins must be designed to permit repeat systemic administration. This review outlines some of the strategies currently being employed in the design of the Viventia Biotech Inc Armed Antibodies to minimize the development of immunogenicity and to remove the potential for toxicity in non-target tissues.