Drug Database
IT

itolizumab

✓ Approved

Siam Bioscience · CD6 · Monoclonal Antibodies

What is itolizumab?

itolizumab is a monoclonal antibodies developed by Siam Bioscience. It is approved for therapeutic indications via injectable (others).

Drug Profile

CompanySiam Bioscience
Drug ClassMonoclonal Antibodies, Antibody
Molecular TargetCD6
RouteInjectable (Others)
StatusApproved
Sources: ClinicalTrials.gov, Siam Bioscience

Mechanism of Action

Molecular Targets

itolizumab acts on 1 molecular target:

CD6CD6 molecule (TP120)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

itolizumab is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Skin and subcutaneous tissue disordersPsoriasis✓ Approved
Musculoskeletal and connective tissue disordersRheumatoid arthritisPhase I

Related Research Articles

PubMedJournal for immunotherapy of cancer2026-10-07

Targeting CD6 in solid tumors: safety, early efficacy, and mechanistic insights from a proof-of-concept trial of itolizumab.

González Muñoz Cynthia C, Ruiz-Lorente Raiza R, Blanco-Pita Olivia O, Lara-Fernández Noralys N et al.

CD6 is a promising target in cancer immunotherapy, with preclinical evidence supporting its role in modulating immune responses. This warrants further investigation into current CD6-targeting treatments, which could lead to new anti-tumor therapies. However, the clinical effects of targeting CD6 in solid tumors remain unexplored. This proof-of-concept study is the first in-human evaluation of the safety and early effectiveness of anti-CD6 monoclonal antibody itolizumab in patients with advanced, highly heterogeneous solid tumors. Treatment had two phases: induction and maintenance. In induction, group A received 100 mg weekly for nine doses; group B received 200 mg biweekly for five doses. After completing induction, patients moved to maintenance 21 days later, receiving 100 mg every 21 days for up to six doses. The primary endpoint was safety; secondary objectives included disease control, survival, and exploratory molecular mechanisms and blood biomarkers. Itolizumab demonstrated a favorable safety profile, with no safety-related treatment discontinuations, no related serious adverse events, and no unexpected toxicities. In this heavily treated, non-biomarker-selected population, disease control was achieved in 25% in group A and 20% in group B, and the 1-year survival rate was 26% in group A and 15% in group B. Mechanistically, ex vivo analysis demonstrated that itolizumab downregulates CD6, increasing soluble CD6 levels and promoting a cytotoxic phenotype on CD8 and NK cells. Additionally, patient-derived peripheral blood mononuclear cells demonstrated boosted in vitro killing capacity specifically against CD318+ cancer cells. The antibody also modulates PD-1 expression in peripheral lymphocytes, promoting NK cell activity while maintaining inhibitory signals on CD8+ T cells and decreasing T helper overactivation. These findings support the dual role of itolizumab, enhancing anti-tumor responses while preventing autoimmune-like effects by reducing off-target inflammation and avoiding immune-related adverse effects associated with immune checkpoint therapies. Overall, these findings support further development of itolizumab as a rational immunomodulatory strategy with a favorable safety profile for advanced solid tumors, particularly in CD318-expressing tumors and as part of rational combination regimens. RPCEC00000444.

PMID 42843925
Read full article →
PubMedJournal of autoimmunity2026-07-22

Itolizumab targets the CD6-ALCAM axis to limit T-cell responses and brain barrier diapedesis in multiple sclerosis.

González-Muñoz Cynthia C, Baeten Paulien P, Hermans Doryssa D, Hoeks Cindy C et al.

Genetic and preclinical data highlight CD6 as a promising target for multiple sclerosis (MS), yet the impact of clinically available CD6-targeting treatments on MS immunopathogenesis remains insufficiently defined. Itolizumab, a humanized anti-CD6 antibody with established safety and clinical efficacy in other autoimmune disorders, represents a potential candidate to interrogate this pathway in MS. CD6 expression was quantified by flow cytometry on circulating lymphocytes from MS patients and healthy donors. Functional consequences of CD6 blockade using itolizumab were evaluated using human in vitro models of brain barriers, including T cell diapedesis, barrier integrity, and inflammatory responses. T cell co-cultures with an oligodendrocyte cell line were performed to reveal the impact on survival and differentiation. Circulating lymphocytes from MS patients displayed increased CD6 levels, associated with heightened activation and proliferation features in CD4+ memory T cells. In brain barrier assays, migrated T cells exhibited higher CD6 expression than non-migrated cells. CD6 blockade with itolizumab selectively reduced memory and cytotoxic T cell diapedesis across hCMEC/D3 monolayers, while maintaining naïve and regulatory T cell migration, by disrupting interaction with ALCAM but not CD318, attenuating cytokine-driven upregulation of endothelial adhesion molecules, and strengthening BBB integrity. Itolizumab limited the retention and acquisition of a disease-promoting CD69+TRM phenotype in migrated CD4+ T cells, while attenuating their activity in the CNS, thereby promoting oligodendrocyte survival and differentiation. These findings provide mechanistic support for targeting CD6 in MS with itolizumab as a promising therapeutic strategy to reduce neuroinflammation and pathogenic T cell accumulation in the CNS.

PMID 42480393
Read full article →
PubMedWorld journal of virology2025-06-27

COVID-19 management in patients with comorbid conditions.

Sanyaolu Adekunle A, Okorie Chuku C, Marinkovic Aleksandra A, Prakash Stephanie S et al.

The novel coronavirus disease 2019 (COVID-19) causes serious respiratory illness and related disorders. Vulnerable populations, including those with chronic obstructive pulmonary disease, heart disease, diabetes, chronic kidney disease, obesity, and the elderly, face an increased risk of severe complications. As the pandemic evolves, various diagnostic techniques are available to detect severe acute respiratory distress syndrome (SARS-CoV-2), including clinical presentation, rapid antigen/antibody testing, molecular testing, supplemental laboratory analysis, and imaging. Based on peer-reviewed data, treatment options include convalescent plasma transfusion, corticosteroids, antivirals, and immunomodulatory medications. Convalescent plasma therapy, historically used in outbreaks like Middle East respiratory syndrome, Ebola, and SARS, is suggested by the World Health Organization for critically ill COVID-19 patients when vaccines or antiviral drugs are unavailable. Neutralizing antibodies in convalescent plasma help control viral load and improve patient outcomes, especially when administered early, though effectiveness varies. The United States Food and Drug Administration has authorized its emergency use for severe COVID-19 cases, but potential risks such as transfusion reactions and transfusion-related acute lung injury require further investigation to establish definitive efficacy. Antiviral agents like Remdesivir, an adenosine nucleotide analog, inhibit viral RNA polymerase and have shown efficacy in reducing COVID-19 severity, leading to its emergency use authorization for hospitalized patients. Other antivirals like ritonavir, lopinavir, and umifenovir disrupt viral replication and entry, but their effectiveness against SARS-CoV-2 remains under investigation. Dexamethasone, a corticosteroid, has been used in critically ill COVID-19 patients to reduce inflammation and prevent respiratory failure, as shown in the RECOVERY trial. Other immunosuppressants like ruxolitinib, baricitinib, and colchicine help modulate the immune response, reducing cytokine storms and inflammation-related complications. However, corticosteroids carry risks such as hyperglycemia, immunosuppression, and delayed viral clearance, requiring careful administration. Systematic reviews of clinical studies revealed that hydroxychloroquine with or without azithromycin did not decrease viral load nor reduce the severity of symptoms, but increased mortality among acutely hospitalized patients. There was no improvement in patients' clinical conditions after 15 days compared to standard treatment. The United States Food and Drug Administration has revoked the authorization for the use of hydroxychloroquine in COVID-19 patients due to the null benefit-risk balance. Monoclonal antibodies like itolizumab, gimsilumab, sarilumab, and tocilizumab are being studied for their ability to reduce the severe inflammatory response in COVID-19 patients, particularly cytokine release syndrome and acute respiratory distress syndrome. These antibodies target specific immune pathways to decrease pro-inflammatory cytokines, with some showing promising results in clinical trials, though their use remains under investigation. The Clustered Regularly Interspaced Short Palindromic Repeats/Cas13 family of enzymes, sequenced from many COVID-19-positive patients, can potentially inhibit SARS-CoV-2 replication, cleave the RNA genome, and aid in the amplification of the genome assay. Cas13 can also target emerging pathogens via an adeno-associated virus vector when delivered to the infected lungs. In addition to pharmacological agents, vaccines effectively prevent symptomatic infection, reduce hospitalizations, minimize mortality rates, and ultimately reduce the severity of the disease. This paper aims to explore the management of patients with underlying conditions who present with COVID-19 to lessen the burden on healthcare systems.

PMID 40575645
Read full article →
PubMedFrontiers in immunology2025-05-20

Itolizumab regulates activating and inhibitory signals on effector cells, improving their cytotoxicity against CD318+ tumor cell lines.

González Muñoz Cynthia C, Álvarez Arzola Rydell R, Calvo Pérez Adanays A, Frometa Campanón Milagro de la Caridad MC et al.

The CD6-CD318 axis has emerged as a potential target for immuno-oncology. Recent work has shown that blocking the CD6-CD318 interaction with a murine anti-human CD6 antibody increases lymphocyte cytotoxicity. However, several studies have demonstrated the drawbacks associated with the clinical use of murine antibodies and the variability among anti-CD6 antibodies. Therefore, evidence that the first-in-class humanized anti-human CD6 antibody itolizumab could be used for cancer immunotherapy may be a breakthrough in developing an antitumor clinical approach. Phenotypic and functional characterization of peripheral blood mononuclear cells (PBMCs) from healthy donors after challenge with CD318+ cell lines was performed by flow cytometry. In addition, IFNγ was determined by ELISA in culture supernatants. Immunohistochemical analyses of breast tumor samples were also performed. Here, we provide evidence supporting the rationale for itolizumab in cancer immunotherapy. The blockade of the CD6-CD318 interaction by itolizumab increases the cytotoxic capacity of CD8 T and NK cells over CD318+ tumor lines, reverses the NKG2A/NKG2D ratio, and increases granzyme B and IFNγ production. Itolizumab also regulates immune responses by downregulating CD5 expression and upregulating PD-1 and CTLA-4 inhibitory receptors on lymphocytes, which contribute to reducing exacerbated responses and additively enhancing CD318+ tumor cell cytotoxicity when combined with other immunocheckpoint inhibitors. In addition, we report that CD6-CD318 interaction inhibits lymphocyte proliferation and survival while downregulating CD6 expression on lymphocytes in vitro and in human breast cancer tissue samples, reinforcing the role of the CD6-CD318 axis as an immune checkpoint and highlighting the potential of itolizumab as an immune checkpoint inhibitor. Taken together, our results provide the first evidence linking the blocking of the CD6-CD318 axis by itolizumab with the potentiation of functional properties of lymphocytes, highlighting itolizumab as a novel promising immunotherapy for CD318+ tumors and supporting the relevance of new combinatorial therapies with checkpoint inhibitors.

PMID 40391211
Read full article →
PubMedAcute and critical care2024-12-03

Corrigendum to: Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study.

Kumar Abhyuday A, Kumar Neeraj N, Pattanayak Arunima A, Kumar Ajeet A et al.

PMID 39622603
Read full article →
PubMedCurrent hematologic malignancy reports2024-11-13

Contemporary Updates in the Prevention and Treatment of Graft-Versus-Host Disease.

Abedin Sameem S, Hamadani Mehdi M

Graft-versus-host disease (GVHD) is a serious complication after allogeneic HCT. Recently, several pivotal studies have been conducted demonstrating significant improvements in the management of GVHD. Here, we review important trials pertaining to GVHD prevention, acute GVHD treatment, and treatment of steroid refractory acute and chronic GVHD. Clinical trials in preventing GVHD demonstrate lower rates of severe acute GVHD and chronic GVHD with post-transplant cyclophosphamide. For acute GVHD, lower risk acute GVHD appears amenable to steroid-sparing therapies, such as sirolimus and itacitinib. Combinations with novel agents such as itolizumab appear promising for high risk acute GVHD. For steroid-refractory acute GVHD, ruxolitinib should be considered first line therapy. For chronic GVHD requiring therapy beyond steroids, ruxolitinib, belumosudil, and ibrutinib are now available and should be considered. Increasingly, GVHD has become a manageable complication after allogeneic HCT potentially translating to greater success with allogeneic HCT in the future.

PMID 39520614
Read full article →

+63 more articles available with a free account

Sign up free to view all articles →

Ask about itolizumab