Anti-CD6 mAbs for the treatment of psoriasis

Dogra, Sunil; Shabeer, D; Rajagopalan, Murlidhar

doi:10.1080/14712598.2020.1776254

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…CD6 is expressed by lymphocytes and facilitates the interaction between T cells and APCs, resulting in the secretion of inflammatory mediators such as TNF-α, IFN-α and IL-6. CD6-deficient mice develop an attenuated psoriasis-like skin inflammation [ 25 , 28 ]. Based on this knowledge, inhibiting anti-CD6 antibodies were successfully used for the treatment of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Dietary Fatty Acids in an Open-Label Study Improves Psoriasis and Dampens the Inflammatory Activation Status

et al. 2023

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Obesity and high abdominal fat mass are risk factors for developing the chronic inflammatory skin disease psoriasis. They are associated with increased incidence, prevalence and severity of the disease. A positive effect of weight loss on psoriasis activity has been shown in several studies. Obesity-related factors such as the dysregulation of glucose and lipid metabolism, the activation of adipose tissue and resultant persistent low-grade inflammation have been discussed as links of obesity and inflammatory diseases. Recently, we demonstrated a critical role of free fatty acids (FFAs) in obesity-mediated exacerbation of psoriatic skin inflammation in both mice and humans. In the present study, we translated these findings into a therapeutic intervention. An open-label study focusing on the dietary reduction of FFAs was conducted in patients with mild-to-moderate plaque psoriasis, and disease severity and serum markers of inflammation were analyzed. Here, we show that such a dietary intervention improves psoriatic disease activity independently of weight loss. Diet-related metabolic changes, such as a reduction in saturated free fatty acids (SFAs), may thus be more important than weight loss itself. Moreover, dietary intervention inhibited the overall pro-inflammatory activation status in patients, as shown by analysis of serum inflammatory parameters using the Olink platform. From our pilot study, we conclude that dietary intervention focusing on SFA reduction has the capacity to reduce disease activity and general inflammatory status in psoriasis patients.

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Section: Discussionmentioning

confidence: 99%

Modulation of Dietary Fatty Acids in an Open-Label Study Improves Psoriasis and Dampens the Inflammatory Activation Status

et al. 2023

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“…In this context and despite the lack of a thorough understanding of CD6 function, availability of mouse and humanized anti-CD6 mAbs has provided valuable information regarding the potential targeting of CD6 for the treatment of RA, psoriasis and potentially other T cell-driven autoimmune conditions [119]. Indeed, ALZUMAb ® (Itolizumab), a humanized anti-human CD6 mAb developed from its parent murine antibody IOR-T1, has been approved by the Drugs Controller General of India in January 2013 to treat psoriasis [120,121]. A randomized phase III clinical trial was carried out in India in a cohort of 225 patients with moderate to severe chronic psoriasis plaques in which Itolizumab was effective and well-tolerated [122].…”

Section: Soluble Cd6 As Therapeutic Agent In Autoimmunitymentioning

confidence: 99%

Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents

Andrés

Casadó-Llombart

Català

et al. 2020

Cells

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CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, respectively). To serve such a relevant immunomodulatory function, the extracellular region of CD5 and CD6 interacts with soluble and/or cell-bound endogenous counterreceptors but also microbial-associated molecular patterns (MAMPs). Evidence from genetically-modified mouse models indicates that the absence or blockade of CD5- and CD6-mediated signals results in dysregulated immune responses, which may be deleterious or advantageous in some pathological conditions, such as infection, cancer or autoimmunity. Bench to bedside translation from transgenic data is constrained by ethical concerns which can be overcome by exogenous administration of soluble proteins acting as decoy receptors and leading to transient “functional knockdown”. This review gathers information currently available on the therapeutic efficacy of soluble CD5 and CD6 receptor infusion in different experimental models of disease. The existing proof-of-concept warrants the interest of soluble CD5 and CD6 as safe and efficient immunotherapeutic agents in diverse and relevant pathological conditions.

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“…Itolizumab has been approved in India for the treatment of moderate-to-severe chronic plaque psoriasis since 2013 [ 17–20 ]. It has shown promising results in managing psoriatic arthritis [ 21 , 22 ] and rheumatoid arthritis [ 23 , 24 ] in addition to a favorable safety profile in Phase 2 and Phase 3 trials. Based on the periodic reviews of safety data, the overall safety profile evaluation for Itolizumab has remained consistent over the years.…”

Section: Introductionmentioning

confidence: 99%

A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19

Kumar

Souza

Nadkar

et al. 2021

Expert Opinion on Biological Therapy

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Objective : Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study. Methods : Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment. Results : Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = −0.3 [−0.61, −0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events. Conclusion : Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

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Anti-CD6 mAbs for the treatment of psoriasis

Cited by 8 publications

References 51 publications

Modulation of Dietary Fatty Acids in an Open-Label Study Improves Psoriasis and Dampens the Inflammatory Activation Status

Modulation of Dietary Fatty Acids in an Open-Label Study Improves Psoriasis and Dampens the Inflammatory Activation Status

Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents

A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19

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