Inclusion
1\. Documented informed consent of the participant
2\. Willingness to continue into follow-up assessments for up to 15 years after autoCD6-CAR Treg treatment
3\. Willingness to wear a study continuous glucose monitoring device (CGMD) for 2 weeks prior to mandated study visits for at least 1 year of follow-up post last CAR Treg infusion.
4\. Age: 18-35 years old
5\. Stage 3 T1D diagnosed by standard ADA Criteria, with residual beta cell function, enrolled between 12 and 24 months from the date of T1D diagnosis.
Historical or current presence of at least one type-1 diabetes associated autoantibody other than insulin autoantibodies, such as:
Must have stimulated C-peptide levels ≥ 0.2 nmol/L measured during a 2-hr mixed meal tolerance test (MMTT) conducted prior to enrollment.
Willing to comply with intensive diabetes management.
6\. Negative Covid-19 self-antigen test within 3 days of enrollment.
7\. Vaccinations: Participants are required to be fully vaccinated for age.
Subjects should have immunizations as recommended for age by the CDC
Participants must be at least 90 days from last live immunization.
8\. Must be willing to not use any non-insulin glucose-lowering agents such as GLP-1 agonists (including for weight loss indication), symlin, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas). Participants are required to go off these drugs 30 days prior to screening.
9\. Deemed able to correctly use the study CGMD following training session with Certified Diabetes Educator (CDE).
10\. Absolute neutrophil counts (ANC) ≥ 1,000/mm3
11\. Leukocytes ≥ 2500/mL
12\. Platelets ≥ 100,000/mm3
13\. Hemoglobin ≥ 10 g/dL
14\. Lymphocytes ≥ 800/mm3
15\. Total bilirubin ≤ 2.0 X ULN
16\. AST ≤ 2.0 x ULN
17\. ALT ≤ 2.0 x ULN
18\. Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
19\. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
20\. Seronegative for HIV Ag, HCV\*, and active HBV (Surface Antigen Negative)\*\*
21\. Subjects must have negative QuantiFERON-TB Gold (QFTG) test. Patients with positive QFTG test need clearance from ID before enrollment.
22\. Negative for CMV, EBV by PCR-based assay
23\. Meets other institutional and federal requirements for infectious disease titer requirements.
24\. Agreement by women of child bearing potential (WOCBP), who are not currently pregnant, to avoid pregnancy and breastfeeding, and to undergo pregnancy testing at baseline and prior to each cell product administration, and on further follow-up for the duration of the study.
25\. Agreement by women of childbearing potential (WOCBP) and males of childbearing potential\* to use an effective\*\* method of birth control\*\* from screening through 1 year of follow-up from the last dose of study treatment.
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Highly effective birth control is defined as use of an intrauterine device (IUD), combination of two methods that are user dependent of which only one can be a barrier method, or true abstinence from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, declaration of abstinence for the duration of the study, withdrawal, and lactational amenorrhea are not acceptable methods of contraception. Some hormonal contraceptives may interact with the investigational drug or affect study results. Generally, stable use of hormonal contraceptive/s for at least 6 months is recommended, or as otherwise deemed appropriate by PI..
Any lab abnormality believed to be transient may be repeated at the discretion of the site PI. If repeat value does not preclude participation, and potential participant would otherwise qualify for the study, then may proceed with enrollment per investigator discretion.
Exclusion
1\. Prior treatment with Itolizumab or other CD6-directed therapies.
2\. Prior or current participation in research study in which a potential participant received an immunomodulatory agent or diabetes care, unless the participant was in the placebo arm.
3\. Other investigational agents, biologics (including cellular immunotherapies)
4\. Anti-inflammatory therapy (Exception: Over-the-counter (OTC) anti-inflammatory agents (e.g. ibuprofen, Tylenol) are generally allowed)
5\. Systemic corticosteroids within 14 days prior to leukapheresis
6\. Systemic immunosuppressive therapy (e.g., cyclosporine-A, cyclophosphamide)
7\. Vaccine(s) within 8 weeks of leukapheresis
8\. Prior organ transplant
9\. Last dose of Beta-cell stimulants (e.g., sulphonylureas), glucagon-like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors, insulin sensitizers (e.g., metformin, thiazolidinediones), verapamil, must be at least 30 days prior to enrollment.
10\. Unstable cardiac disease as defined by one of the following:
11\. Uncontrolled arrhythmia and/or coronary artery disease
12\. Cardiac events such as myocardial infarction (MI) within the past 6 months
13\. NYHA (New York Heart Association) heart failure class III-IV
14\. Uncontrolled atrial fibrillation or hypertension
15\. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
16\. History of stroke or intracranial hemorrhage within 6 months prior to screening
17\. Other autoimmune/inflammatory disorders except:
18\. Active infection requiring hospitalization or intravenous antibiotics and/or anti-virals
19\. Any history of HIV.
20\. Known positive test result for chronic HBV infection (defined by HBsAg positivity).
21\. Antiviral prophylaxis may be administered as per institutional guidelines
22\. History of prior malignancy within 5 years of enrollment with the exception of the following:
23\. Clinically significant uncontrolled illness
24\. Females only: pregnant or breastfeeding
25\. Any other condition (including psychosocial condition, medical issues, or lab abnormalities) that would, in the Investigator's judgment, contraindicate/interfere with the patient's participation in the clinical study or cause increased risk to pre-existing disease, due to safety concerns with clinical study procedures / treatment.
26\. Any other condition (such as hypersensitivity reaction to study medications/components) that would confound study results
Any lab abnormality believed to be transient may be repeated at the discretion of the site PI. If repeat value does not preclude participation, and potential participant would otherwise qualify for the study, then may proceed with enrollment per investigator discretion.