Autologous CD45 base-edited stem cells plus CART-45 cells for relapsed or refractory hematologic cancers

Inclusion Criteria:

1\. Signed informed consent form 2. Male or females age ≥ 18 years 3. Disease-Specific Criteria

a. B-cell Non-Hodgkin Lymphoma (B-cell NHL)- including the following sub-types:

i. Patients with any of the following large B-cell lymphoma diagnoses who meet the prior treatment criteria outlined below: Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS); Primary Cutaneous DLBCL; Primary Mediastinal (thymic) Large B-cell Lymphoma; ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); High-grade B-cell Lymphoma, NOS; T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; or any aggressive B-cell lymphoma arising from indolent lymphoma.

1\. Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND 2. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy.

ii. Follicular Lymphoma

1. Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
2. Relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy).

iii. Mantle Cell Lymphoma

1. Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
2. Relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.

   iv. Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Note: Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.

   b. T-cell Non-Hodgkin Lymphoma (T-cell NHL)

   i. Histologically or cytologically confirmed relapsed or refractory (r/r) mature aggressive T- and NK-cell neoplasms as defined in the 5th edition of the WHO Classification of Hematolymphoid tumors, which includes any of the following diagnoses:

   • Peripheral T-cell Lymphoma, NOS (PTCL-NOS);

   • Nodal T-cell Lymphomas with T Follicular Helper \[TFH\] Phenotype, including Follicular T cell Lymphoma, Angioimmunoblastic Lymphoma, or Anaplastic Large Cell Lymphoma (ALCL);

   • ALK+ or ALK-, Enteropathy-Associated T-cell Lymphoma (EATL);

   • Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL);

   • Extranodal NK/T-cell Lymphoma;

   • Primary Cutaneous T-cell Lymphoma (CTCL);

   • Transformed Mycosis Fungoides (tMF) without blood involvement;

   • Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma;

   • Subcutaneous Panniculitis-like T-cell Lymphoma.

   ii. Must have received at least one prior line of systemic therapy for their lymphoma. Additional prior treatment provisions required for the following indications:

1\. Participants with Anaplastic Large Cell Lymphoma (ALCL) must have received prior Brentuximab vedotin, unless contraindicated.

2\. Participants with Subcutaneous Panniculitis-like T-cell Lymphoma or Transformed Mycosis Fungoides (tMF) must have received at least 2 prior lines of systemic therapy.

c. Hodgkin Lymphoma (HL)

i. Patients with histologically proven classical Hodgkin Lymphoma that is CD45 positive by IHC or flow cytometry by a CLIA certified laboratory; AND

ii. Relapsed/refractory disease after at least 2 prior lines of therapy which must include the following:

1. Brentuximab vedotin and immune checkpoint inhibitors (unless contraindicated); AND
2. Autologous stem cell transplant (unless patient has chemorefractory disease to salvage treatment) d. Large Cell Transformation of CLL (Richter's Transformation) i. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.

4\. Patients are appropriate candidates for autologous HSCT as per physician-investigator clinical discretion

5\. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:

a. Have no active GVHD and require no immunosuppression

b. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility

6\. Adequate organ function defined as:

1. Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis
2. ALT/AST ≤ 3 x ULN
3. Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl
4. Left Ventricular Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
5. DLCO \> 45% predicted value; adjusted for level of hemoglobin
6. Must have minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air 7. ECOG Performance Status 0-1

Exclusion Criteria:

1. Active hepatitis B or hepatitis C infection
2. Any active, uncontrolled infection.
3. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
4. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
5. Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
6. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
7. Active acute or chronic GVHD requiring systemic therapy.
8. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
9. Active CNS involvement. Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
10. Patients with evidence of a circulating T-cell malignancy as measured by flow cytometry.
11. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
12. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
13. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.