NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)

Inclusion Criteria:

- 1. Subjects with a confirmed diagnosis of relapsed refractory multiple myeloma (MM),
melanoma, synovial sarcoma, or myxoid/round cell liposarcoma (MRCL) as follows:

a. Multiple Myeloma i. Subjects must have a confirmed prior diagnosis of active MM as
defined by the International Myeloma Working Group (IMWG) criteria.

ii. Subjects must have relapsed or refractory disease after either one of the following:

1. At least 3 prior regimens, which must have contained an alkylating agent, proteasome
inhibitor, and immunomodulatory agent (IMiD) OR

2. At least 2 prior regimens if "double-refractory" to a proteasome inhibitor and IMiD,
defined as progression on or within 60 days of treatment with these agents.

Note: Induction therapy, stem cell transplant, and maintenance therapy, if given
sequentially without intervening progression, should be considered as 1 "regimen".

iii. Subjects must be at least 90 days since autologous stem cell transplant, if performed.

iv. Toxicities from prior therapies, with the exception of alopecia or peripheral
neuropathy attributable to bortezomib, must have recovered to grade ≤ 2 according to the
Common Toxicity Criteria (CTCAE) 4.0 criteria or to the subject's prior baseline.

v. Subjects must have measurable disease per IMWG criteria on study entry, which must
include at least 1 of the following:

1. Serum M-spike ≥ 0.5 g/dL*

2. 24 hour (hr) urine M-spike ≥ 200mg

3. Involved serum free light chain (FLC) ≥ 50 mg/L with abnormal ratio

4. Measurable plasmacytoma on exam or imaging

5. Bone marrow plasma cells ≥ 20%

- Note: Patients with IgA myeloma in whom serum protein electrophoresis is deemed
unreliable, due to co-migration of normal serum proteins with the paraprotein in
the beta region, may be considered eligible as long as total serum IgA level is
elevated above normal range.

b. Melanoma i. Subjects must have a confirmed prior diagnosis of melanoma. ii.
Progressed after at least 2 therapy lines. iii. Subjects with BRAF mutant tumors
should have received and progressed through, or are intolerant to, BRAF/MEK
inhibitor therapy prior to enrollment iv. Patients must have measurable disease
per RECIST 1.1 in order to allow assessment of an anti-tumor response.

c. Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (MRCL) i. Subjects must have
a confirmed prior diagnosis of synovial sarcoma or MRCL. ii. Patients with proven
metastatic disease or surgically inoperable local recurrence that have failed
first line treatment.

iii. Patients must have measurable disease per RECIST 1.1 in order to allow assessment of
an anti-tumor response.

- 2. Provides written, informed consent.

- 3. Subjects ≥ 18 years of age.

- 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- 5. Documented NY-ESO-1 and/or LAGE-1 expression on tumor tissue.

- 6. HLA-A*201 positive

- 7. Subjects of reproductive potential must agree to use acceptable birth control
methods, as described in protocol Section 4.3.

- 8. Adequate vital organ function as defined by:

1. Serum creatinine ≤ 2.5 or estimated creatinine clearance ≥30 ml/min and not
dialysis-dependent.

2. Absolute neutrophil count ≥1000/μl and platelet count ≥50,000/μl (≥30,000/μl if
bone marrow plasma cells are ≥50% of cellularity for MM patients).

3. Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3x the upper limit of normal and
total bilirubin ≤ 2.0 mg/dl (except for patients in whom hyperbilirubinemia is
attributed to Gilbert's syndrome).

4. Left ventricular ejection fraction (LVEF) ≥ 45%. LVEF assessment must have been
performed within 8 weeks of eligibility confirmation by physician-investigator.

Exclusion Criteria:

- 1. Pregnant or nursing (lactating) women.

- 2. Have inadequate venous access for or contraindications to leukapheresis.

- 3. Have any active and uncontrolled infection.

- 4. Active hepatitis B or hepatitis C

- 5. Human immunodeficiency virus (HIV) infection.

- 6. Any uncontrolled medical or psychiatric disorder that would preclude participation
as outlined.

- 7. New York Heart Association (NYHA) Class III or IV heart failure, unstable angina,
or a history of recent (within 6 months) myocardial infarction or sustained (>30
seconds) ventricular tachyarrhythmias.

- 8. Received prior gene therapy or gene-modified cellular immunotherapy. Subject may
have received, however, non-gene-modified autologous T-cells in association with an
anti-myeloma vaccine (e.g., hTERT or MAGEA3) or vaccination against infectious agents
(e.g., influenza or pneumococcus) as was performed on our previous studies.

- 9. Active auto-immune disease, including connective tissue disease, uveitis,
sarcoidosis, inflammatory bowel disease, or multiple sclerosis, or have a history of
severe (as judged by the principal investigator) autoimmune disease requiring
prolonged immunosuppressive therapy.

- 10. Prior allogeneic stem cell transplant.

- 11. Prior or active central nervous system (CNS) involvement (e.g. leptomeningeal
disease, parenchymal masses) with myeloma. Screening for this (e.g. with lumbar
puncture) is not required unless suspicious symptoms or radiographic findings are
present. Subjects with calvarial disease that extends intracranially and involves the
dura will be excluded, even if cerebrospinal fluid (CSF) is negative for myeloma.