LymphoCide Y-90 (epratuzumab Y-90) / Gilead - LARVOL DELTA

Treg fitness signatures as a biomarker for disease activity in Juvenile Idiopathic Arthritis. (PubMed, J Autoimmun) - "Three Treg clusters were of interest in active JIA PB, including TIGIThighCD226highCD25low Teff-like Tregs, CD39-TNFR2-Helioshigh, and a 4-1BBlowTIGITlowID2intermediate Treg cluster predominated in inactive JIA PB (AJC = 0)...Thus, we demonstrate altered Treg signatures and subsets as an important factor, and useful biomarker, for disease progression versus remission in JIA, revealing genes and proteins contributing to Treg fitness. Ultimately, PB Treg fitness measures could serve as routine biomarkers to guide disease and treatment management to sustain remission in JIA."

Biomarker • Journal • Idiopathic Arthritis • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • ENTPD1 • TIGIT

CD22 modulation alleviates amyloid β-induced neuroinflammation. (PubMed, J Neuroinflammation) - "The pivotal therapeutic potential of targeting CD22 was demonstrated in Amyloid β (Aβ) induced-neuroinflammation in hCD22 transgenic mice...Intriguingly, we discovered that CD22 interact with Aβ and suciraslimab enhanced internalization of CD22-Aβ complex in microglia. Our data highlights the importance of sCD22 in driving neuroinflammation and the dual mechanism of targeting CD22 to resolve Aβ-induced inflammation and promote Aβ phagocytosis."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CCL3 • CD22 • IL12A • IL1B • IL23A • IL6 • TNFA

IL-18 primes T cells with an antigen-inexperienced memory phenotype for proliferation and differentiation into effector cells through Notch signaling. (PubMed, J Leukoc Biol) - "Moreover, inclusion of γ-secretase inhibitors attenuated the effect of IL-18 on both proliferation and interferon-γ production in the cells. These results demonstrate that IL-18 primes CD44highCD122highCXCR3highCD62LhighCD8+ T cells for expansion and differentiation into effector cells in a Notch signaling-dependent manner."

IO biomarker • Journal • Oncology • CCR7 • CD5 • CD8 • CXCR3 • IFNG • IL18 • IL2 • IL2RA • KIT • MYC • NOTCH1 • PD-1

Targeting CD22 on Memory B Cells to Induce Tolerance to Peanut Allergens. (PubMed, J Allergy Clin Immunol) - "Antigen-specific exploitation of CD22 on memory B cells can induce systemic immune tolerance."

Journal • Allergy • Food Hypersensitivity • Immunology • CD22

Genetically encoded multivalent liquid glycan array displayed on M13 bacteriophage. (PubMed, FASEB J) - "LiGA is target agnostic and measures binding profile of lectins expressed on intact cells, such as hCD22 (Siglec-2) and DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin), and in live mice (Nat...Additionally, we explored the roles of valency and density in ganglioside interaction with Siglec-1 using a cell-based assay. Building on these successes, we plan to use LiGA to identify the valency and affinity required by trans- glycan to overcome the cis- masking on the surface of immune cells."

Journal • Oncology • CD22

Exploiting CD22 on Memory B Cells to Induce Tolerance to Peanut Allergens (AAAAI 2022) - "Antigen-specific exploitation of CD22 on memory B cells can induce systemic immune tolerance in multiple model systems, highlighting the therapeutic potential of CD22L-STALs in peanut allergy."

Late-breaking abstract • Allergy • Food Hypersensitivity • Immunology • CD22

Efficacy and Safety of Sequential Different B Cell Antigen-Targeted CAR T-Cell Therapy for Pediatric Refractory/Relapsed Burkitt Lymphoma with Secondary Central Nervous System Involvement (ASH 2021) - "The patients who achieved an ongoing complete response (CR) did not receive further therapy; for patients who retained a partial response (PR) or no response (NR) until m CD19 CAR T cells became undetectable in PB by flow cytometry (FCM), the second hCD22 CAR T-cell infusion was initiated so that it did not prematurely interfere with the antitumor effect of m CD19 CAR T cells, and could prevent disease progression in the setting of continuous m CD19 CAR T-cell contraction; and for patients who had progressive disease (PD) or relapsed disease (RD) after responding to m CD19 CAR T cells, considering that the tumor had already produced immune escape from m CD19 CAR T cells, regardless of whether there were m CD19 CAR T cells detectable in PB by FCM, the second hCD22 CAR T-cell infusion was immediately initiated. CONCLUSION S equential CAR T-cell therapy may result in a durable response and is safe in pediatric r/r Burkitt lymphoma. Patients with secondary CNS involvement..."

CAR T-Cell Therapy • Clinical • Burkitt Lymphoma • Hematological Malignancies • Immunology • Lymphoma • Oncology • Pediatrics • CD19 • CD20 • CDKN1A

2021 ESMO Review | Gastrointestinal Cancers | Colorectal (YouTube) - "From Total Health's 2021 ESMO Virtual Review on October 23-24, 2021, we bring you a session on colorectal cancer treatment updates presented by Dr. Cathy Eng...In the session, Eng covers Phase III AstezoTRIBE; role of Y-90 in 2nd line mCRC: EPOCH; role of molecular correlates with DESTINY CRC-01 trial; and role of TMZ + IO in mCRC (MAYA Trial)."

Video

Roundtable Discussion: Finn Explores Treatment for Unresectable HCC (Targeted Oncology) - "SAAB: If she has fatty liver [and] if we were convinced [the disease was] noncirrhotic, I may biopsy. But with the AFP that high, unless the patient had vesicular cancer, I'm not sure what would cause AFP that high. FINN: Unlikely in a woman-other germ cell tumors. Part of the issue is that some cholangiocarcinomas can also express AFP. It's not so specific. What if it was an LR4 lesion? LR4 is still 60% to 70% likely to be liver cancer. Let's say we have the same patient with cirrhotic LR4; would you recommend a biopsy then?"

Media quote

Late-Breaking Data Demonstrate Improved Progression-Free Survival in Patients with Metastatic Colorectal Cancer After Treatment with Boston Scientific TheraSphere Y-90 Glass Microspheres (PRNewswire) - '"The EPOCH trial not only demonstrated positive safety and efficacy data for the patients treated in this study, but underscores the success of integrating a device-based therapy like TheraSphere treatment in the continuum of care with systemic chemotherapy and biologic regimens, thereby providing the rationale and setting the stage for future investigation in other cancer types,' said Riad Salem...of the EPOCH trial."

Media quote

[VIRTUAL] New drugs for low grade lymphoproliferative diseases (EHOC 2020) - "For symptomatic patients or for those with high tumor burden, initial treatment is usually chemoimmunotherapy with an anti-CD20 monoclonal antibody (mo-Ab), most commonly Rituximab or Obinutuzumab plus an alkylator, such as bendamustine or chlorambucil and/or a pourine analog, such as fludarabine or cladribine...Newer anti-CD20 mo-Abs, such as Ublituximab appear equally effective, but have not yet been tested comparatively with the previous ones. Radioconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab are no more in broad use due to unpredicted myelotoxicity. The newer 90Y-epratuzumab tetratexan appears safe as consolidation following R-CHOP in DLBCL patients. Polatuzumab vedotin, Pinatuzumab vedotin and Tafasitamab targeting CD19 have mainly been used, combined with an anti-CD20 mo-Ab to treat RR-DLBCL with success, which render them candidates for indolent lymphomas also...Acalabrutinib, already approved for CLL/SLL and MCL, is now being tested for other..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatology • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CRBN • EZH2 • SYK

Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Immunomedics, Inc.; N=70 ➔ 0; Active, not recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20

Efficient elimination of primary B-ALL cells in vitro and in vivo using a novel 4-1BB-based CAR targeting a membrane-distal CD22 epitope. (PubMed, J Immunother Cancer) - "We report a novel, high-affinity hCD22.7 scFv which targets a membrane-distal epitope of CD22. 4-1BB-based hCD22.7-CAR T cells efficiently eliminate clinically relevant B- CD22 and CD22 ALL primary samples in vitro and in vivo. Our study supports the clinical translation of this hCD22.7-CAR as either single or tandem CD22-CD19-CAR for both naive and anti-CD19-resistant patients with B-ALL."

IO Biomarker • Journal • Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Hematological Malignancies • Leukemia • Oncology

Combination Veltuzumab and Fractionated 90Y- Epratuzumab Radioimmunotherapy in Follicular Lymphoma (clinicaltrials.gov) - P1/2; N=5; Active, not recruiting; Sponsor: Weill Medical College of Cornell University; Recruiting ➔ Active, not recruiting; N=20 ➔ 5

Enrollment change • Enrollment closed • Biosimilar • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Immunomedics announces third quarter fiscal 2012 results and clinical program developments (Immunomedics) - P1/2, N=70; IM-T-hA20/90Y-hLL2-01; Initial clinical experience of 90Y-labeled epratuzumab combined with veltuzumab in pts with aggressive lymphoma will be reported in an oral presentation at the 59th Annual Meeting of the Society of Nuclear Medicine (SNM) on Wed, Jun 13, 2012

Anticipated P1/2 data presentation • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Immunomedics reports updated clinical results on potential new treatment regimens for non-Hodgkin lymphoma (ASH 2012, Immunomedics) - P2, N=75; "Immunomedics...reported that small, repeated doses of epratuzumab labeled with the radioisotope, yttrium-90 (90Y), demonstrated therapeutic activity in 2 clinical trials in patients with aggressive non-Hodgkin lymphoma (NHL)...the overall response rate (ORR) after 6 cycles of R-CHOP therapy was 94.6% (71/75), with 52 patients (69.3%) achieving a complete or unconfirmed complete response (CR/CRu) and 19 patients (25.3%) reporting a partial response (PR)...For the 61 patients who received the 2 consolidation 90Y-epratuzumab treatments, ORR was 91.8% (56/61), with 50 patients (81.9%) achieving a CR/CRu."

P2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Immunomedics reports updated clinical results on potential new treatment regimens for non-Hodgkin lymphoma (ASH 2012, Immunomedics) - P2, N=75; "Immunomedics...reported that small, repeated doses of epratuzumab labeled with the radioisotope, yttrium-90 (90Y), demonstrated therapeutic activity in 2 clinical trials in patients with aggressive non-Hodgkin lymphoma (NHL)...the overall response rate (ORR) after 6 cycles of R-CHOP therapy was 94.6% (71/75), with 52 patients (69.3%) achieving a complete or unconfirmed complete response (CR/CRu) and 19 patients (25.3%) reporting a partial response (PR)...For the 61 patients who received the 2 consolidation 90Y-epratuzumab treatments, ORR was 91.8% (56/61), with 50 patients (81.9%) achieving a CR/CRu."

P2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

RITEPRALL: Study Evaluating the Efficacy of 90Yttrium-epratuzumab in Adults With CD22+ Relapsed/Refractory B-ALL (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Nantes University Hospital; N=69 ➔ 0; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Sep 2020 ➔ Jan 2017

Enrollment change • Trial primary completion date • Trial withdrawal • Acute Lymphocytic Leukemia • Biosimilar • Lymphoma

Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL (clinicaltrials.gov) - P1/2; N=70; Active, not recruiting; Sponsor: Immunomedics, Inc.; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 dose-escalation study of ⁹⁰yttrium-labeled anti-CD22 epratuzumab tetraxetan in adults with refractory/relapsed CD22+ B-cell acute lymphoblastic leukemia (B-ALL) (ASH 2014) - Presentation time: Monday, December 8, 2014, 6:00 PM-8:00 PM; Abstract #3708; P1, N=20; NCT01354457; "⁹⁰Y-DOTA-hLL2 RIT is well-tolerated and induced complete remissions even in heavily pre-treated CD22⁺ relapsed/refractory B-ALL patients, thus appearing to be a promising targeted therapy for CD22⁺ B-ALL. We recommend the dose of 10 mCi/m² given twice, one week apart/cycle, for phase 2 studies."

P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies

Immunomedics reports updated clinical results on potential new treatment regimens for non-Hodgkin lymphoma (ASH 2012, Immunomedics) - P1/2, N=70; NCT01101581; "Results from 18 patients with various types of aggressive NHL who had failed 1 or more prior standard therapies were reported at the conference...The overall objective response rate among 17 patients who have had treatment response assessments was 53%, including one DLBCL patient (6%) with a CR continuing 12 months later. The combination is active in all NHL subgroups and across 90Y dose levels. At the maximum tolerated dose of 6 mCi/m2 x 2, 5 of 6 patients (83%) achieved PRs."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Immunomedics reports updated clinical results on potential new treatment regimens for non-Hodgkin lymphoma (ASH 2012, Immunomedics) - P1/2, N=70; NCT01101581; "Results from 18 patients with various types of aggressive NHL who had failed 1 or more prior standard therapies were reported at the conference...The overall objective response rate among 17 patients who have had treatment response assessments was 53%, including one DLBCL patient (6%) with a CR continuing 12 months later. The combination is active in all NHL subgroups and across 90Y dose levels. At the maximum tolerated dose of 6 mCi/m2 x 2, 5 of 6 patients (83%) achieved PRs."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Aberrant expression of β5t in the periphery induces a self-reactive T-cell response (IMMUNOLOGY 2020) - "In β5i-/-β5t-Tg mice, the percentage of naïve　CD44lowCD122low was reduced, and the percentage of memory CD44highCD122high CD8+ T cells was significantly elevated. These results demonstrate that the aberrant peripheral expression of β5t disrupts the maintenance of a naïve pool of CD8+ T cells and induces autoreactive T-cell responses. The self-peptides generated by β5t are required to confine in the thymus to avoid autoimmunity in the peripheral tissues, and self-peptides mimicking β5t-producing peptides in the periphery may cause the failure of immunological regulation and tolerance."

IO Biomarker • CD44 • CD8 • PD-1

Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5. (PubMed, Proc Natl Acad Sci U S A) - "...Here, we present a unique side-by-side arrangement pattern of two tandem immunoglobulin V-set (IgV) domains deriving from the ectodomains of both human CD226 (hCD226-ecto) and mouse CD226 (mCD226-ecto), which is substantially different from the conventional head-to-tail arrangement of other multiple Ig-like domain molecules...In the absence of the D2 domain, CD226-D1 exhibited substantially reduced binding efficacy to CD155. Collectively, these findings would broaden our knowledge of the interaction between NK cell receptors and the nectin/Necl family ligands, as well as provide molecular basis for the development of CD226-targeted antitumor immunotherapeutics."

Journal