Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands

General eligibility criteria:

* ECOG performance status 0 or 1.Patients with multiple myeloma who have an ECOG performance status of 2 based on peripheral neuropathy from prior therapies are eligible.
* Ability to understand and the willingness to sign a written informed consent document.
* Pathological confirmation of AML, MDS-RAEB or Multiple myeloma.
* Agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CM-CS1 CART-cell administration.
* Ability to adhere with the study visit schedule and other protocol procedures.
* Willingness to remain within a 50 mile radius of Brigham Women's Hospital during the initial 10 days following CM-CS1 infusion

Disease specific eligibility criteria for patients with AML, MDS-RAEB:

* Pathological confirmation of AML, MDS-RAEB according to WHO classification (CMML is excluded) that is not in remission (defined as \>5% blasts in bone marrow or peripheral blood) and for which there are no reasonable standard treatment options.
* No known or suspected CNS disease. A neurologic exam is required and signs or symptoms suggestive of potential CNS disease require CNS imaging.
* Disease status deemed not to require additional therapy for at least 4 weeks from enrollment.
* Life expectancy of greater than 4 weeks.
* Participants must have satisfactory organ function as defined below:

  1. Total bilirubin ≤2.0 × institutional upper limit of normal (Except for subjects with known Gilbert's syndrome)
  2. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
  3. Creatinine ≤ 2.0 mg/dL

Disease specific eligibility criteria for patients with multiple myeloma:

* Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria.
* Relapsed or relapsed/refractory multiple myeloma with progressive disease
* Presence of measurable disease as defined as one or more of the following:

  1. Serum M-protein \>0.5g/dl
  2. Urine M-protein \> 200mg/24hr
  3. Serum FLC assay: involved FLC level \> 10mg/dl with abnormal serum FLC ratio
  4. Measurable plasmocytoma in non-secretory patients.
* Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
* Life expectancy of greater than 12 weeks
* No known or suspected CNS involvement. A neurologic exam is required and signs or symptoms of potential CNS involvement require CNS imaging. Peripheral neuropathy is acceptable.
* Participants must have satisfactory organ and marrow function as defined below:

  1. Absolute neutrophil count \> 500/mcL. Screening ANC should be independent of G-CSF and GM-CSF support for at least 1 week and of pegylated G-CSF for at least 2 weeks
  2. Platelets \>20,000/mcL. Subjects may receive platelet transfusions, if clinically indicated, in accordance with institutional guidelines.
  3. Total bilirubin ≤2.0 × institutional upper limit of normal. (Except patients with known Gilbert's syndrome)
  4. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
  5. Creatinine ≤ 2.0 mg/dL

Exclusion Criteria:

* Participants who have received chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
* Concurrent systemic steroid or other immunosuppressive therapy.
* Participants who are concurrently receiving any other investigational agents, or have received another investigational agent within 3 weeks before enrollment.
* Participants who have received prior allogeneic stem cell transplantation, gene therapy, or adoptive T-cell therapy.
* Active infections necessitating use of treatment antibiotics/antivirals during the screening period (prophylaxis is acceptable) or evidence of an active communicable infectious disease.
* Participants who underwent major surgery within 4 weeks before day 0 of planned CM-CS1 T-cell infusion (this does not include placement of vascular access device or tumor biopsies).
* Participants with any known history of primary immunodeficiency.
* History of allergic reactions or hypersensitivity attributed to Human serum albumin or Plasma-lyte A.
* Uncontrolled intercurrent illness or serious uncontrolled medical disorder
* Pregnancy or breastfeeding
* Known HIV-positive participants are ineligible because the effect of transducing HIV-infected lymphocytes with the chimeric NKG2D- transgene on the disease course is unknown.
* Clinically relevant active infection including active hepatitis B or C or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study.
* Active autoimmune disease
* History of a malignancy other than one of the malignancies in this study with exception of the following circumstances:

  1. Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded.
  2. Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are not excluded.
* Unwillingness to use an effective contraceptive method during the study and at least 4 months after administration of CM-CS1 T-cells unless subject is naturally infertile.