The risks associated with taking blood draw samples are pain, bruising, or infection. RISK/BENEFIT ANALYSIS Because all patients in this prot ocol have metastatic or recurr ent/refractory locally advanced cancer and limited life expectanci es the potential benefit is thought to outweigh the potential risks. CONSENT PROCESS AND DOCUMENTATION If the patient meets the thorough screening for eligibility, the patient, with family members or friends at the request of the patient, will be presented with a detailed description of the protocol treatment. The specific requi rements, objectives, and potential advantages and disadvantages will be presented. The informed consen t document is given to the patie nt, who is requested to review it and to ask questions prior to ag reeing to participate in the treatment portion of t his protocol. The patient is reassu red that participati on on trial is entirely voluntary and that he/she can withdraw or decide against tr eatment at any time without advers e consequences. The Principal Investigator, associate investig ator, or clinical fellow is resp onsible for obtaining written consent from the patient. 10.6.1 Informed Consent of Non -English Speaking Subjects If there is an unexpected enrollme nt of a research participant for whom there is no translated extant IRB approved consent docum ent, the Principal Investigato r and/or those authorized to obtain informed consent will use th e Short Form Oral Consent Pro cess as described in MAS Policy M77-2, OHSRP SOP 12, 45 CFR 46.117 (b) (2), and 21 CFR 50. 27 (b) (2). The summary that will be used is the Englis h version of the extant IRB appr oved consent document. Signed copies of both the English versi on of the consent and the trans lated short form will be given to the subject or their legally aut horized representative and the signed original w ill be filed in the medical record. Unless the PI is fluent in the pr ospective subject’s language, an interpreter will be present to facilitate the conversation (using either the long translated f orm or the short form). Preferably someone who is independent of the subject (i.e., not a family m ember) will assist in presenting information and obtaining consent . Whenever possible, interpret ers will be provided copies of the relevant consent documents w ell before the consent conversa tion with the subject (24 to 48 hours if possible). We request prospective IRB appr oval of the use of the short for m process for non-English speaking subjects and will notify the IRB at the time of contin uing review of the frequency of the use of the Short Form.11 PHARMACEUTICAL INFORMATION CELLPREPARATION The procedure for growing and expanding the autologous DC and th e Certificate of Analysis are similar to those approved by the Food and Drug Administration a nd used in other NCI SB clinical studies. This product will be provided f or investigati onal use only under a Sponsor IND. The Certificate of Analysis is in Appendix 2 andAppendix 3 , and the Standard Operating Abbreviated Title: Personalized DC Vaccine Version Date: March 26, 2018 41Procedures for the growth of de ndritic cells is in the IND and i n the NCI SB BB Master File 13782. DC will be administered at a dose of between 1x107to 8x107dendritic cells. SUBCUTANEOUS INJECTION AND INTRAVENOUS INFUSION PREPARATION Classification: Peptide Loaded Dendritic Cell Vaccine Mode of Action: Autologous monocyte derived DC pulsed with peptide neoantigens a re recognized in vivo by tumor-specific cytotoxic T-lymphocytes, l eading to a major histocompatibility complex-restri cted cytotoxic response agains t tumor cells bearing these neoantigens. Product Description: The vaccine is derived from auto logous DCs produced ex vivo from monocytes isolated from an aphe resis product. DCs are produced u sing clinical grade cytokines (IL-4 and GM-CSF). Neoantigens w ill be identified from a sequence comparison of a patient’s tumor and normal DNA sample. An alg orithm will predict mutated sequences with a high probability of binding to a patient’s specific HLA repertoire. Neoantigens will be prepared as peptides, either as 25mers, wit h the mutated amino acid residue situated at position 13, or as minimal epitopes. The patient’s tumor infiltrating lymphocytes, cultured from a biopsy sample or PBMC, will be screened for their ability to recognize these pre dicted neoantigens pulsed onto DCs. Neoantigens recognized by the patient’s TIL or PBMC will b e used to formulate the vaccine. The vaccine will be formulated for each administration as follows. The identified peptides will be pulsed onto thawe d, previously cryopreserved DCs overnight. The following day, the DCs pulsed with peptides will be matured with Poly I:C, R848 and IFN- J(TLR mix). The DCs will be washed and 1-8x107will be loaded into syringes for IV and SQ administration. How Supplied: Neoantigen Peptides: The peptides will be manufactured by Peptid es and Elephants (PE) GmBH, Potsdame, Germany. The peptides are suppli ed as a sterile, GLP grade, lyophilized powder (TFA salt) in vials. Interferon- Jis purchased from Miltenyi as a lyophilized powder. Poly I:C will be purchas ed from a qualified supplier as a lyophilized powder. R848 will be purchased from a qualified s upplier as a lyophilized powder. Preparation: Peptides for pulsing DCs will be reconstituted in sterile water for DC pulsing to a final concentration of 1 mg/mL. Poly I:C is reconstituted in st erile water at a concentration of 1mg/ml. R848 is reconstituted in ste rile water for injection at a concentration of 1mg/mL. Interferon- Jis reconstituted in ster ile water for injection at a concentrat ion of 4x106units per mL. Storage: Peptides for Pulsing: Lyophilize d vials will be stored at -20°C . Reconstituted peptide solutions will be stored at -20°C . DCs will be cryopreserved in Cryostor10 and maintained in vapor phase liquid nitrogen (-140 to -180°C) until used. Poly I :C and R848 are stored at -20°C as lyophilized powders and as recons tituted solutions. Interferon- Jis stored as lyophilized powder at -20°C and as a recons tituted solution at 4°C. Stability: The peptides, Poly I:C, R848 and D C are stable at the recommended storage temperatures for at least one year. Interferon- Jwill be made up fresh for each maturation process. The long-term stabilit y of these vaccine components is under evaluation through an on- going stability testing program. Route of Administration:SQ Injection: A total of 1 mL (0.5 to 4x10 7) DCs will be administere d as an injection into the deep SQ tissue of a proximal extr emity. Injections will preferentially be administered in the Abbreviated Title: Personalized DC Vaccine Version Date: March 26, 2018 42anterior thigh. Injections w ill not be given into extremities t hat have had radical lymph node dissections. The same extremity will be used for each cycle of the peptide loaded dendritic cell vaccine administration. IV Infusion: A total of (0.5 to 4x107) cells for IV administration will be infused over 20-30 minutes via non-filtered tubing, ge ntly agitating the bag durin g infusion to prevent cell clumping. Potential Adverse Events and Risks: The peptide antigens pulse d on to the DCs will be unique to each patient and may mimic por tions of natural proteins foun d naturally throughout the body, there is a chance for the development of autoimmune reactions t o cells containing these proteins. Special Handling: The peptides are NOT a cytotoxic or infectious agent and require no special handling. The DCs are a blood derived product. All personnel should treat blood derived products as potentially infectious material. Universal precauti ons and infection control should be practiced at all times. Abbreviated Title: Personalized DC Vaccine Version Date: March 26, 2018 4312 REFERENCES 1. 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