Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis

Boden, Elisa K.; Canavan, James B.; Moran, Christopher J.; McCann, Katelyn; Dunn, William A.; Farraye, Francis A.; Ananthakrishnan, Ashwin N.; Yajnik, Vijay; Gandhi, Roopali; Nguyen, Deanna D.; Bhan, Atul K.; Weiner, Howard L.; Korzenik, Joshua R.; Snapper, Scott B.

doi:10.1093/crocol/otz009

Cited by 13 publications

(10 citation statements)

References 27 publications

(33 reference statements)

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“…In the first study of six patients with moderate-to-severe ulcerative colitis who received oral anti-CD3 antibody, it was shown that it was well tolerated by all subjects. Nonetheless, it was not correlated with a change in Treg-associated molecule expression, namely Foxp3 and CTLA-4 ( 166 ). Currently, Foralumab (28F11-AE; NI-0401) is the only fully human anti-CD3 mAb ( 167 ).…”

Section: Role In Autoimmunitymentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

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Section: Role In Autoimmunitymentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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“…The biological mechanism of UC is the induction of regulatory T cells through anti-CD3 antibody uptake in gut-associated lymphoid tissue. Orally delivered muromonab-CD3 improved symptoms in the colon of patients with UC in a phase 2 trial using omeprazole, a proton pump inhibitor (NCT01287195) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Delivery of Orally Administered Digestible Antibodies Using Nanoparticles

Tashima

2021

IJMS

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Oral administration of medications is highly preferred in healthcare owing to its simplicity and convenience; however, problems of drug membrane permeability can arise with any administration method in drug discovery and development. In particular, commonly used monoclonal antibody (mAb) drugs are directly injected through intravenous or subcutaneous routes across physical barriers such as the cell membrane, including the epithelium and endothelium. However, intravenous administration has disadvantages such as pain, discomfort, and stress. Oral administration is an ideal route for mAbs. Nonetheless, proteolysis and denaturation, in addition to membrane impermeability, pose serious challenges in delivering peroral mAbs to the systemic circulation, biologically, through enzymatic and acidic blocks and, physically, through the small intestinal epithelium barrier. A number of clinical trials have been performed using oral mAbs for the local treatment of gastrointestinal diseases, some of which have adopted capsules or tablets as formulations. Surprisingly, no oral mAbs have been approved clinically. An enteric nanodelivery system can protect cargos from proteolysis and denaturation. Moreover, mAb cargos released in the small intestine may be delivered to the systemic circulation across the intestinal epithelium through receptor-mediated transcytosis. Oral Abs in milk are transported by neonatal Fc receptors to the systemic circulation in neonates. Thus, well-designed approaches can establish oral mAb delivery. In this review, I will introduce the implementation and possibility of delivering orally administered mAbs with or without nanoparticles not only to the local gastrointestinal tract but also to the systemic circulation.

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“…In a book on this subject, symptoms of anaphylaxis such as pyrexia (90 %; 40.0 °C or higher in 19 % of cases), chills (59 %), dyspnea (21 %), nausea and vomiting (19 %), chest pain (14 %), diarrhea (14 %), tremor (13 %), bronchospasm (13 %), headache (11 %), tachycardia (10 %), stiffness (8 %), and hypertension (8 %) were reported [148]. Pilot studies of this drug have been performed orally in patients with moderate to severe ulcerative colitis [149]. In this study, no severe side effects or CRS have been reported.…”

Section: Muromonabmentioning

confidence: 99%

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

Gülşen¹,

Wedi²,

Jappe³

2020

Allergo J

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Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). Conclusion: There is an urgent need for a simpler symptom-or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future. Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

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Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis

Cited by 13 publications

References 27 publications

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

Delivery of Orally Administered Digestible Antibodies Using Nanoparticles

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

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