GRP78 chimeric antigen receptors and combination therapies for treating cancer

Abstract

Immunotherapies, particularly chimeric antigen receptors (CARs) targeting GRP78, and their use for treating cancer are provided. Also provided are nucleic acids encoding the CARs, vectors including the nucleic acids encoding the CARs, and immune cells expressing the CARs. Also provided are methods of treating a subject with cancer, including administering to the subject a GRP78 immunotherapy and a combination chemotherapy including a HSP90 inhibitor and a multikinase inhibitor.

Description

[0001]7213-109906-02GRP78 CHIMERIC ANTIGEN RECEPTORS AND COMBINATION THERAPIES FOR TREATING CANCER CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No.63 / 460,549, filed April 19, 2023, which is incorporated by reference in its entirety. FIELD This disclosure relates to cancer immunotherapies and combination cancer therapies. INCORPORATION OF ELECTRONIC SEQUENCE LISTING The Sequence Listing is submitted as an XML file named “Sequence.xml,” created on March 28, 2024, 29,544 bytes, which is incorporated by reference herein. ACKNOWLEDGMENT OF GOVERNMENT SUPPORT This invention was made with government support under AI130197 and CA267368 awarded by The National Institutes of Health. The government has certain rights in the invention. BACKGROUND Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers in humans. Multikinase inhibitor-resistance (MKIR) is a major challenge for the treatment of HCC and is the leading cause of cancer mortality. Immunotherapy (e.g., adoptive cell transfer, monoclonal antibodies, and immune checkpoint inhibitors) is a safer and more precise alternative to chemotherapy, however, immunotherapy has had limited success for treating HCC. Maximum survival with immunotherapy treatment is only 4 months longer than chemotherapy counterparts (15 months vs.11 months). The limited success may be due in part to production of immunosuppressive cytokines by cancerous cells, such as TGF-β, which silence immune responses of cytotoxic T cells and NK cells (e.g., shedding of activating ligands like MICA / B or overexpressing inhibitory ligands like PD-L130-33). Despite recent efforts to improve immunotherapy responses by reducing the immunosuppressive microenvironment of tumors, there remains a lack of effective treatment options for HCC patients. It is estimated that 90% of HCC patients are resistant to both immunotherapy and chemotherapy due to the complex, constantly changing mutational landscapes of tumor cells. Thus, novel treatment strategies are greatly needed. Tumors experience continuous environmental stress, such as hypoxia and pH changes, that normally induce apoptosis or immune cell-mediated clearance in non-cancerous cells. However, tumor cells can bypass this vulnerability to environmental stress by utilizing Heat Shock Protein (HSP) chaperones. Heat Shock Proteins include cytosolic and membrane-bound chaperones that assist in protein homeostasis under7213-109906-02stress conditions. Specifically, Heat Shock Protein 90 (HSP90), Heat Shock Protein 70 (HSP70), and ER- paralogs (GP94, GRP78), desensitize cancer cells to environmental stressors. HSP90 and its co-chaperone HSP70 support the “chaotic” cancer proteome, which includes a vast repertoire of mutant / dysfunctional proteins like mutant p53. HSP90 also promotes evolution of drug resistance by stabilizing misfolded proteins that are still functional, though not responsive to small-molecule inhibitors. While HSP90 inhibition can sensitize various cancers to treatments such as chemotherapy, checkpoint inhibitors, or radiation therapy, no HSP90 inhibitor has demonstrated sufficient efficacy to achieve FDA approval. Limited efficacy can be attributed in part to the dose-limiting toxicity of the drug. While high-level inhibition of HSP90 is well tolerated acutely, sustained and near complete signaling inhibition is required for anti-cancer efficacy, leading to the activation of cytoprotective heat shock responses. In addition, high-level inhibition of HSP90 has been shown to suppress both innate and adaptive immunity. Glucose Regulated Protein 78 (GRP78) is a heat-shock protein that resides in the endoplasmic reticulum. GRP78 assists in protein homeostasis by stabilizing misfolded proteins. Under stress condition, GRP78 can translocate to the surface of cells. Cell-surface GRP78 is associated with poor disease prognosis and has been implicated in tumor cell plasticity, immune evasion, and chemoresistance. Immunotherapies (e.g., ACT, monoclonal antibodies, checkpoint inhibitors, etc.) provide precise tumor targeting by enhancing cell-mediated killing of tumors. Natural Killer (NK) cell-based therapies have been shown to successfully target various cancer subtypes. Recent clinical trials have shown superior clinical safety of CAR-NK cells as compared to CAR-T cells. CAR-NK cells are allogeneic, secrete fewer tissue-damaging cytokines, and cannot induce Graft Versus Host Disease and Cytokine Release Syndrome with proper T cell depletion in patients prior to treatment. Another benefit of CAR-NK cells is that they have a large repertoire of receptors for tumor detection. However, CAR-NK based therapies are not very effective at targeting MKIR-HCC due to cirrhosis associated immune dysfunction and tumor burden. SUMMARY Disclosed herein are chimeric antigen receptors that specifically bind and / or target GRP78. The CARs include (a) an extracellular domain; (b) a transmembrane domain; and (c) an intracellular domain that includes one or more signaling domains. The extracellular domain includes a binding portion that specifically binds GRP78. In some examples, the binding portion is or includes a GRP78 binding peptide (e.g., SEQ ID NO: 1). In some implementations, the extracellular domain includes a tag, for example, an IgG1 tag. Also disclosed are nucleic acid molecules encoding the chimeric antigen receptor disclosed herein or a GRP78 expression cassette that includes an IL-15 domain, as well as vectors including such nucleic acid molecules. Also disclosed are host cells expressing a CAR disclosed herein, or that include nucleic acids disclosed herein, or vectors including such nucleic acids. In some examples, the host cell is used to express / produce a protein (e.g., a CAR disclosed herein), or express / produce viruses, for example, a virus7213-109906-02encoding a CAR or GRP78 expression cassette disclosed herein. In some examples, the host cell is a 293T cell. In some examples, the host cell is an immune cell, for example, a NK cell, T cell, or NKT cell. Further disclosed are pharmaceutical compositions including CARs, nucleic acids, vectors, or host cells as disclosed herein, and a pharmaceutically acceptable carrier. The disclosed compositions are useful for treating cancer, for example, a cancer that expresses GRP78 and / or a solid tumor. Also disclosed are methods of producing GRP78 CAR immune cells, including transforming a population of immune cells with a nucleic acid or vector disclosed herein. In some examples, the immune cell is a NK cell and the method is a method of producing GRP78 CAR-NK cells. Further disclosed are methods of treating cancer in a subject, including administering to the subject an effective amount of (a) a HSP90 inhibitor, (b) a multikinase inhibitor, and (c) a GRP78 immunotherapy. In some examples, the HSP90 inhibitor and multikinase inhibitor are administered to the subject before the GRP78 immunotherapy is administered, for example, 1 to 7 days before the GRP78 immunotherapy is administered. In some examples, the HSP90 inhibitor and multikinase inhibitor are administered as an adjuvant chemotherapy for 72 hours, followed by administration of GRP78 immunotherapy for at least three treatment cycles. In some examples, the GRP78 immunotherapy is an adoptive cell therapy (ACT) and includes a chimeric antigen receptor (CAR) that specifically binds GRP78, e.g., a GRP78 CAR disclosed herein. In some examples, the GRP78 immunotherapy is a GRP78 CAR-NK cell therapy. The HSP90 inhibitor can include, for example, STA-9090, BIIB021, 17-AAG, or SNX-2112. In some examples, the multikinase inhibitor includes regorafenib, sorafenib, or lenvatinib. In a non-limiting example, the HSP90 inhibitor is STA-9090, the multikinase inhibitor is regorafenib, and the GRP78 immunotherapy is a GRP78 CAR-NK cell immunotherapy. In some examples, the subject has a solid tumor. In some examples, the subject has lung, liver, breast, or pancreatic cancer. In some examples, the cancer expresses cell surface GRP78. The foregoing and other features, of the disclosure will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures. BRIEF DESCRIPTION OF THE FIGURES FIGS.1A-1C show that combination therapy of ganetespib (STA-9090) with a multikinase inhibitor (sorafenib or regorafenib) decreases viability of hepatocellular carcinoma and pancreatic ductal adenocarcinoma cell lines. Cisplatin (NSC 119875), a common therapy for many solid tumor types, shows minimal efficacy in treating hepatocellular carcinoma, with no change when combined with STA-9090. This suggests synergistic effects in the VEGFR-pathway and rejects alternative additive effects of using HSP90 inhibitor with other drugs. FIG.1A shows percent cell viability of a hepatocyte control cell line (Hu1545) following a 72-hour incubation with the indicated treatments. FIG.1B shows percent cell viability of MKIR-HCC following a 72-hour incubation with the indicated treatments. FIG.1C shows percent cell viability of several MKI-resistant pancreatic ductal adenocarcinoma cell lines (Panc1, BXPC3 and MiaPaca2) and control cell line Hu1545 following a 72-hour incubation with the indicated treatments7213-109906-02(Veh= vehicle; Cis= cisplatin; Sora= sorafenib; Regor= regorafenib). Values are Mean ± SEM normalized to the vehicle. Significant P-values are shown above the bars; NS = not significant. FIGS.2A-2C show that VEGFR2 total protein and phosphorylation is reduced in MKIR-HCC cells following incubation with regorafenib and STA-9090 (STA+Regor). Hepatocyte control or MKIR-HCC cells were incubated for 72 hours with the indicated treatments (Veh= vehicle; Regor= regorafenib monotherapy; STA= STA-9090 monotherapy; STA+Regor= combination therapy). Samples were collected and probed by Western blot for phospho-VEGFR2, total VEGFR2, phopho-S6RP, phospho-Mek1 / 2, total Akt, and β-actin (control). FIG.2A shows the Western blot and FIGS.2B and 2C show the normalized expression values. FIGS.3A-3B show that HSP90 inhibition stabilizes MICA / B on the surface of MKIR-HCC cell lines with no effects on peripheral blood mononuclear cells (PBMCs). FIG.3A shows fold-change of surface MICA / B detected by flow cytometry upon HSP90 inhibitor-enhanced regorafenib chemotherapy in MKIR-HCC. FIG. B shows fold-change of surface MICA / B detected by flow cytometry upon HSP90 enhanced regorafenib chemotherapy in PBMCs. Values shown are Mean ± SEM normalized to vehicle. Significant P-values are indicated above the bars. NS= not significant. FIG.4 shows a representative flow cytometry of expanded NK cells using the feeder-based expansion system. FIGS.5A-5B show that HSP90 inhibitor therapy has minimal toxicity in vitro on expanded healthy NK cells. The figures show PI-AnnexinV- staining of CD56+expanded NK cells after 48-hour incubation with the indicated treatments. No significant reductions in cell viability were found after treatment with STA-9090 (FIG.5A) or BIIB021 (FIG.5B). FIG.6 shows that HSP90 inhibitor combination therapy has minimal effects on expanded NK cell survival and function. The figure shows normalized Annexin-V (a cell death marker) positive cells after incubating NK cells for 5 hours with combination therapy pretreated MKIR-HCC. Values shown are Mean ± SEM across three donors. T-test was performed on Means (*P< 0.05, **P<0.01, ***P < 0.001, NS = non- significant). FIGS.7A-7B show GRP78 surface expression of the indicated cell types detected by flow cytometry. FIG.7A shows percent (%) positive cells while FIG.7B shows Mean Fluorescence Intensity (MFI). Significantly higher expression of GRP78 was found across HCC and PDAC cell lines as compared to expanded CD3+T cells. Values shown are Mean ± SEM compared to expanded CD3+ T cells. P-values are indicated above the bars. FIGS.8A-8B shows GRP78 (BiP) surface expression after a 72-hour incubation in a hepatocyte control (FIG.8A) or MKIR-HCC (FIG.8B) cell line. Percent (%) positive cells are shown on the left, Mean Fluorescence Intensity (MFI) is shown on the right. Significantly higher GRP78 expression was found in tumor cells as compared to non-tumor cells. Values shown are Mean ± SEM compared to vehicle. P-values are indicated above the bars.7213-109906-02FIG.9 shows surface GRP78 expression in the indicated mouse tissues after 3 cycles of 72-hour combination chemotherapy. Percent (%) positive cells are shown on the left, Mean Fluorescence Intensity (MFI) is shown on the right. FIGS.10A-10B show a schematic of constructs transduced into expanded NK cells (FIG.10A), and flow cytometry of the GRP78 CAR-NK cells 10 days post-transduction (FIG.10B). FIGS.11A-11B show viability and expansion of GRP78-CAR-NK cells compared to naïve, untransduced NK cells and CD19 CAR-NK cells. FIG.11A shows percent live cells on days 7, 10, 12, 16 and 20 after retroviral transduction. FIG.11B shows fold expansion from day 0 using a novel 721.221 mIL21 feeder system. Values shown are Mean ± SEM across three donors. T-test was performed on Means (*P< 0.05, **P<0.01, ***P < 0.001, NS = non-significant). FIGS.12A-12B show transduction efficiency across CAR constructs. FIG.12A shows Percent CD56+ CAR+ GRP78-CAR-NK after retroviral transduction across different blood donors. FIG.12B shows fold change of transduction GRP78-CAR-NK, CARD, CD19-CAR-NK from day 0 of transduction. Values shown are Means ± SEM across three donors. T-test was performed on Means (*P< 0.05, **P<0.01, ***P < 0.001, NS = non-significant). FIGS.13A-13C show in vitro killing efficacy of MKI-resistant solid tumors. Chromium-51 release assays were used to compare GRP78 CAR-NK killing to naïve NK killing for various MKI-resistant tumor cell lines (SK-Hep1 (FIG.13A), HCO2 (FIG.13B), and BXPC3 (FIG.13C)). Values shown are Mean ± SEM. P-values are shown on the right. FIG.14 shows representative live imaging following a 24 hour incubation of SK-Hep1 with GRP78-CAR-NK. The light grey signal indicates AnnexinV positive target cells. FIG.15 shows an exemplary treatment timeline for an MKIR-HCC orthotopic tumor model. FIGS.16A-16C show GRP78 CAR-NK in vivo killing efficacy of MKIR-HCC. Mouse weight (FIG.16A), tumor volume (FIG.16B), and survival (FIG.16C) of mice treated with either naïve NK cells or GRP78 CAR-NK cells were followed. Values for individual mice are shown for mouse weight (FIG.16A) and tumor volume (FIG.16B). Mouse survival was significantly increased with GRP78 CAR-NK treatment (FIG.16C, P-value = 0.0224). FIGS.17A-17E show in vivo results of HSP90i-MKI adjuvant chemotherapy in combination with GRP78-CAR-NK immunotherapy. FIG.17A shows the treatment course for the SK-Hep1 engrafted NSG mouse in vivo study. FIG.17B shows survival curves of mice treated with HSP90i and MKI chemotherapy (HSP90i-MKI), GRP78-CAR-NK immunotherapy (GRP78-IL15-CAR-NK), or a combination of HSP90i- MKI chemotherapy and GRP78-CAR-NK immunotherapy (chemo + CAR-NK), as compared to vehicle (PBS+IL2) mice. FIG.17C shows Mean tumor volumes over the course of treatment. Tumor volume was determined by caliper measurements. FIG.17D shows Mean number of metastatic nodules in liver per mouse normalized to liver weight after day 51 of study. FIG.17E shows average tumor weights and representative tumor images from mice compared to vehicle treated group. For survival data, log-rank (Mantel-Cox) test was performed on Means (*P< 0.05, **P<0.01, ***P < 0.001, NS = non-significant). For7213-109906-02other data, values shown are Mean ± SEM across individual mice. T-test was performed on Means (*P< 0.05, **P<0.01, ***P < 0.001, NS = non-significant). FIGS.18A-18C show representative time-lapse IVIS® images (in vitro computed tomography (CT) imaging; FIG.18A) and ROI quantifications (FIGS.18B-18C) of mice undergoing the indicated treatments. FIGS.19A-19D show weight and tumor measurements over the course of treatment. FIGS.19A- 19B shows weight of individual mice during course of study. FIGS.19C-19D shows tumor measurements of individual mice during pre-metastasis (prior to day 51) stage of study. SEQUENCES Any nucleic acid and amino acid sequences listed herein are shown using standard letter abbreviations for nucleotide bases and amino acids, as defined in 37 C.F.R. § 1.822. In at least some cases, only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand. SEQ ID NO: 1 is an exemplary amino acid sequence of a GRP78 binding peptide. CTVALPGGYVRVC SEQ ID NO: 2 is an exemplary amino acid sequence of a human IgG1 tag. EPKSPDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 3 is an exemplary amino acid sequence of a CD28 transmembrane domain. FWVLVVVGGVLACYSLLVTVAFIIFWV SEQ ID NO: 4 is an exemplary amino acid sequence of a CD28 intracellular domain. RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS SEQ ID NO: 5 is an exemplary amino acid sequence of a 4-1BB intracellular domain. KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL SEQ ID NO: 6 is an exemplary amino acid sequence of a CD3ζ intracellular domain. RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQK DKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR SEQ ID NO: 7 is an exemplary amino acid sequence of an E2A-linked IL-15 domain. QCTNYALLKLAGDVESNPGPMRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILGCFSAGLPKTEA NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLII LANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS SEQ ID NO: 8 is an exemplary amino acid sequence of a GRP78 CAR. MEFGLSWLFLVAILKGVQCVDCTVALPGGYVRVCSYVTVSSQDPAEPKSPDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPGKKDPKFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRR7213-109906-02PGPTRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRV KFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR SEQ ID NO: 9 is an exemplary nucleic acid sequence encoding a GRP78 binding peptide. TGCACCGTGGCCCTGCCCGGCGGCTACGTGAGAGTGTGC SEQ ID NO: 10 is an exemplary nucleic acid sequence encoding a human IgG1 tag. GAGCCCAAATCTCCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGG GGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACG TGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACG TACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAG TGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAG GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAACCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTA AA SEQ ID NO: 11 is an exemplary nucleic acid sequence encoding a CD28 transmembrane domain. TTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCT TTATTATTTTTTGGGTG SEQ ID NO: 12 is an exemplary nucleic acid sequence encoding a CD28 intracellular domain. AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGG CCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCC SEQ ID NO: 13 is an exemplary nucleic acid sequence encoding a 4-1BB intracellular domain. AAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACT ACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACT G SEQ ID NO: 14 is an exemplary nucleic acid sequence encoding a CD3ζ intracellular domain. AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTAT AACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGA CCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGC AGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGC AAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTT CACATGCAGGCCCTGCCCCCTCGC SEQ ID NO: 15 is an exemplary nucleic acid sequence encoding an E2A linked IL-15 domain. CAGTGTACTAATTATGCTCTCTTGAAATTGGCTGGAGATGTTGAGAGCAATCCCGGGCCCATGC GGATCAGCAAGCCCCACCTGCGGAGCATCAGCATCCAGTGCTACCTGTGCCTGCTGCTGAACA GCCACTTCCTGACCGAGGCCGGCATCCACGTGTTCATCCTGGGCTGCTTCAGCGCCGGACTGCC CAAGACCGAGGCCAACTGGGTGAACGTGATCAGCGACCTGAAGAAGATCGAGGACCTGATCC AGAGCATGCACATCGACGCCACCCTGTACACCGAGAGCGACGTGCACCCCAGCTGCAAGGTGA CCGCCATGAAGTGCTTTCTGCTGGAACTGCAGGTGATCAGCCTGGAAAGCGGCGACGCCAGCA TCCACGACACCGTGGAGAACCTGATCATCCTGGCCAACAACAGCCTGAGCAGCAACGGCAACG TGACCGAGAGCGGCTGCAAAGAGTGCGAGGAACTGGAAGAGAAGAACATCAAAGAGTTTCTG CAGAGCTTCGTGCACATCGTGCAGATGTTCATCAACACCAGCTGA7213-109906-02SEQ ID NO: 16 is an exemplary nucleic acid sequence encoding a GRP78 CAR. ATGGAGTTTGGGCTGAGCTGGCTTTTTCTTGTGGCTATTTTAAAAgGTGTCCAGTGCGTCGACTG CACCGTGGCCCTGCCCGGcGGCTACGTGAGAGTGTGCTCGTACGTCACCGTCTCTTCACAGGAT CCCGCCGAGCCcAAATCTCCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCC TGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACA GCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGA ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGG AGAGCAATGGGCAACCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCT CCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC GGGTAAAAAAGATCCCAAATTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGC TTGCTAGTAACAGTGGCCTTTATTATTTTTTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACA GTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATG CCCCACCACGCGACTTCGCAGCCTATCGCTCCAAACGGGGCAGAAAGAAACTCCTGTATATAT TCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGAT TTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCC CCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGA GTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGA AGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGT GAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCT CAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC SEQ ID NO: 17 is an exemplary GRP78 CAR expression cassette. ATGGAGTTTGGGCTGAGCTGGCTTTTTCTTGTGGCTATTTTAAAAgGTGTCCAGTGCGTCGACTG CACCGTGGCCCTGCCCGGcGGCTACGTGAGAGTGTGCTCGTACGTCACCGTCTCTTCACAGGAT CCCGCCGAGCCcAAATCTCCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCC TGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTG GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACA GCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGA ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGG AGAGCAATGGGCAACCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCT CCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCC GGGTAAAAAAGATCCCAAATTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGC TTGCTAGTAACAGTGGCCTTTATTATTTTTTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACA GTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATG CCCCACCACGCGACTTCGCAGCCTATCGCTCCAAACGGGGCAGAAAGAAACTCCTGTATATAT TCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGAT TTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCC CCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGA GTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGA AGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGT GAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCT CAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCCAGTG TACTAATTATGCTCTCTTGAAATTGGCTGGAGATGTTGAGAGCAATCCCGGGCCCATGCGGATC AGCAAGCCCCACCTGCGGAGCATCAGCATCCAGTGCTACCTGTGCCTGCTGCTGAACAGCCAC TTCCTGACCGAGGCCGGCATCCACGTGTTCATCCTGGGCTGCTTCAGCGCCGGACTGCCCAAGA CCGAGGCCAACTGGGTGAACGTGATCAGCGACCTGAAGAAGATCGAGGACCTGATCCAGAGC7213-109906-02ATGCACATCGACGCCACCCTGTACACCGAGAGCGACGTGCACCCCAGCTGCAAGGTGACCGCC ATGAAGTGCTTTCTGCTGGAACTGCAGGTGATCAGCCTGGAAAGCGGCGACGCCAGCATCCAC GACACCGTGGAGAACCTGATCATCCTGGCCAACAACAGCCTGAGCAGCAACGGCAACGTGACC GAGAGCGGCTGCAAAGAGTGCGAGGAACTGGAAGAGAAGAACATCAAAGAGTTTCTGCAGAG CTTCGTGCACATCGTGCAGATGTTCATCAACACCAGCTGA SEQ ID NO: 18 is an exemplary GRP78 CAR expression cassette that includes 5’ and 3’ LTRs. AATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATG GAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTG AATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAG ATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAG GGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGA TGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTT CGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTC ACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTC TTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTA CCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGAC CACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGT GTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGG ACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGAC TTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGT GCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCG CCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAG CATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCT AGCCTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCA CAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAAC CTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGAT CAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTccccTACATCGTGACCTGGGAAG CCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTT CCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTA TCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCC CCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAG CTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCA AGAACAACTGGACCGACCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCG CCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCAC CCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGC CGACCCCGGGGGTGGAcCATCCTCTAGACTGCCATGGAGTTTGGGCTGAGCTGGCTTTTTCTTG TGGCTATTTTAAAAgGTGTCCAGTGCGTCGACTGCACCGTGGCCCTGCCCGGcGGCTACGTGAG AGTGTGCTCGTACGTCACCGTCTCTTCACAGGATCCCGCCGAGCCcAAATCTCCTGACAAAACT CACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCC CAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACG TGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATG CCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCC CAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAA GGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAACCGGAGAACAACTAC AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGG ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA ACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAAAAGATCCCAAATTTTGGGTGCT GGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTTT GGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCC CCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTC CAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAAC TACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAAC7213-109906-02TGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCT ATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGG GACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACT GCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGG GCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCC TTCACATGCAGGCCCTGCCCCCTCGCCAGTGTACTAATTATGCTCTCTTGAAATTGGCTGGAGA TGTTGAGAGCAATCCCGGGCCCATGCGGATCAGCAAGCCCCACCTGCGGAGCATCAGCATCCA GTGCTACCTGTGCCTGCTGCTGAACAGCCACTTCCTGACCGAGGCCGGCATCCACGTGTTCATC CTGGGCTGCTTCAGCGCCGGACTGCCCAAGACCGAGGCCAACTGGGTGAACGTGATCAGCGAC CTGAAGAAGATCGAGGACCTGATCCAGAGCATGCACATCGACGCCACCCTGTACACCGAGAGC GACGTGCACCCCAGCTGCAAGGTGACCGCCATGAAGTGCTTTCTGCTGGAACTGCAGGTGATC AGCCTGGAAAGCGGCGACGCCAGCATCCACGACACCGTGGAGAACCTGATCATCCTGGCCAAC AACAGCCTGAGCAGCAACGGCAACGTGACCGAGAGCGGCTGCAAAGAGTGCGAGGAACTGGA AGAGAAGAACATCAAAGAGTTTCTGCAGAGCTTCGTGCACATCGTGCAGATGTTCATCAACAC CAGCTGAACGCGTTAGCATGCACCTCGAGATCGATCCGGATTAGTCCAATTTGTTAAAGACAG GATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTAC GAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCC ACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAA CTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAA CAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGA ATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGA TGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGC CCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCT GTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCA GTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATC CGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGG GGTCTTTCA SEQ ID NO: 19 is an exemplary amino acid sequence of an IGHV3-23_07 immunoglobulin heavy chain variable region signal peptide. MEFGLSWLFLVAILKGVQC SEQ ID NO: 20 is an exemplary nucleic acid sequence of an IGHV3-23_07 immunoglobulin heavy chain variable region signal peptide. ATGGAGTTTGGGCTGAGCTGGCTTTTTCTTGTGGCTATTTTAAAAGGTGTCCAGTGC DETAILED DESCRIPTION I. Terms Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Definitions of common terms in molecular biology may be found in Lewin’s Genes XII, ed. Krebs et al., Jones and Bartlett Learning, 2018 (ISBN 9781284104493); George P. Rédei, Encyclopedic Dictionary of Genetics, Genomics, Proteomics and Informatics, 3rdEdition, Springer, 2008 (ISBN: 1402067534), and other similar references. In case of conflict, the present specification, including explanations of terms, will control. The singular terms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. “Comprising A or B” means including A or B, or A and B. It is further understood that all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or7213-109906-02polypeptides are approximate, and are provided for description. To facilitate review of the disclosure, the following definitions are provided: Adoptive Cell Therapy (ACT): A type of immunotherapy, also known as cellular immunotherapy, that uses immune cells to treat cancer. Examples include tumor infiltrating lymphocyte (TIL) therapy, engineered T cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) therapy. TIL therapy involves harvesting T cells that have infiltrated a tumor, activating and expanding the T cells in vitro, and then re-administering the activated / expanded T cells to a patient. In some examples, the TIL is not a naturally occurring TIL. Engineered TCR therapy involves transforming T cells with a T cell receptor that has been engineered to target a specific cancer antigen (non-naturally occurring). Engineered TCRs allow practitioners to personalize treatment by administering T cells that are reactive to an optimal target for the patient’s specific tumor / cancer. CAR therapy involves the expression of a synthetic antigen receptor, known as a chimeric antigen receptor. An advantage of CARs is their ability to bind to cancer cells even if the target antigen is not presented on the cell surface via an MHC. CARs can be expressed in a variety of immune cells, however, T cells or NK cells are most common. In some examples, the ACT (e.g., TILs, or immune cells expressing an engineered TCR or CAR) specifically targets GRP78. Antibody: A polypeptide ligand that includes at least one variable region that recognizes and binds (for example, specifically recognizes and specifically binds) an epitope of an antigen. The term antibody includes, for example, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antigen binding fragments. Examples of antigen binding fragments include but are not limited to Fv, Fab, Fab', Fab'-SH, F(ab')2, diabodies, linear antibodies, single-chain antibody molecules (e.g., scFv), and multispecific antibodies formed from antibody fragments. Mammalian immunoglobulin molecules are composed of a heavy (H) chain and a light (L) chain, each of which has a variable region, termed the variable heavy (VH) region and the variable light (VL) region, respectively. Together, the VHregion and the VLregion are responsible for binding the antigen recognized by the antibody. There are five main heavy chain classes (or isotypes) of mammalian immunoglobulin, which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Antibodies also include genetically engineered forms, for example, chimeric antibodies (e.g., humanized murine antibodies) and heteroconjugate antibodies (e.g., bispecific antibodies). Specific Binding: An antibody (e.g., scFv) or other binding peptide that “specifically binds” a target (e.g., GRP78) is one that binds a target with high affinity and does not significantly bind off target molecules. In one example, an antibody or binding peptide that specifically binds GRP78 is one that binds substantially to a substrate in which GRP78 is attached, or a biological specimen, for example, a cell expressing cell surface GRP78. A certain degree of non-specific interaction may occur between an antibody or binding peptide and a non-target. Specific binding typically results in greater than 2-fold, for example, greater than 5-fold, greater than 10-fold, or greater than 100-fold increase in the amount of bound antibody or binding peptide (per unit time) to a target protein (e.g., GRP78) or cell or tissue expressing the target protein (e.g., cancerous cells expressing GRP78) as compared to a sample lacking the target protein. A7213-109906-02variety of assays (e.g., enzyme-linked immunosorbent assay (ELISA), competition radioimmunoassay, surface plasmon resonance assays, bio-layer interferometry, etc.) appropriate for selecting antibodies or other binding peptides that specifically bind to a particular protein, e.g., GRP78, have been described. Such assays can also be used to determine binding specificity. Cancer: A disease characterized by abnormal or uncontrolled cell growth. Other features often associated with cancer include metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels, suppression or aggravation of inflammatory or immunological response, invasion of surrounding or distant tissues or organs, for example, lymph nodes. “Metastatic disease” refers to cancer cells that have left the original tumor site and migrated to other parts of the body, for example via the bloodstream or lymph system. Checkpoint Inhibitor: A therapeutic that targets a checkpoint protein. Checkpoint proteins downregulate immune responses to help prevent autoimmunity, however, in the context of cancer, can limit an immune cell’s ability to target and eliminate cancerous cells. When checkpoint proteins are inhibited (e.g., PD-1 blockade) immune cells can better target and kill cancerous cells. Exemplary checkpoint proteins include PD-1 / PD-L1 / PD-L2, and CTLA-4 / B7-1 / B7-2. Exemplary checkpoint inhibitors include ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), atezolizumab (Tencentriq®), avelumab (Bavencio®), durvalumab (Imfinzi®), cemiplimab (Libtayo®), palbociclib (Ibrance®), ribociclib (Kisquali®), and abemaciclib (Verzenio®). Further examples are provided in Qiu et al., Journal of the European Society for Therapeutic Radiology and Oncology, 126(3):450-464, 2018; Visconti et al., J Exp Clin Cancer Res.35(1): 153, 2016; and Mills et al. Cancer Res.77(23): 6489-6498, 2017. Chimeric Antigen Receptor (CAR): A chimeric immune receptor that typically includes an extracellular domain including an antigen-binding portion (e.g., a binding peptide that specifically binds GRP78), a transmembrane domain, and an intracellular domain. In some instances, CARs include additional features, for example, a tag for detection (e.g., an IgG domain) or a signal peptide. The intracellular domain typically includes a signaling domain having an immunoreceptor tyrosine-based activation motif (ITAM), for example, CD3ζ or FcεRIγ. In some instances, the intracellular domain of a CAR includes one or more signaling domains from: CD28, CD3ζ, FcεRIγ, 4-1BB (CD137), ICOS, OX40 (CD134), CD27, and DAP10. In some instances, the transmembrane domain includes a CD28 transmembrane domain. A multispecific CAR is a single CAR molecule that includes at least two antigen-binding domains (e.g., binding peptides or scFvs) that each bind a different antigen or a different epitope on the same antigen. For example, a bispecific CAR refers to a single CAR molecule having two antigen-binding domains that each bind a different antigen. A bicistronic CAR refers to two complete CAR molecules, each containing an antigen-binding moiety that binds a different antigen. In some cases, a bicistronic CAR construct expresses two complete CAR molecules that are linked by a cleavage linker. Immune cells (e.g., T cells or NK cells) expressing a bispecific or bicistronic CAR can bind cells that express both of the antigens to which the binding moieties are directed (see, for example, Qin et al., Blood 130:810, 2017; and WO / 2018 / 213337). Any of these CARs can be used with the methods described herein.7213-109906-02CARs that target cancer-specific ligands are useful to treat cancer. For example, immune cells are obtained from a cancer patient or a donor (e.g., NK cells or T cells), the cells are modified to express a CAR that specifically binds a particular cancer target, and then the modified cells are administered to a patient that has the target cancer. The modified immune cells recognize and kill target cancer cells in the patient. First generation CARs typically included the intracellular domain from the CD3ζ- chain, which is the primary transmitter of signals from endogenous TCRs. Second generation CARs added intracellular signaling domains from various costimulatory protein receptors (e.g., CD28, 4-1BB, ICOS) to the cytoplasmic tail of the CAR to provide additional signals to the host immune cell. Third generation CARs combine multiple signaling domains, for example, CD3ζ / CD28 / 4-1BB or CD3ζ / CD28 / OX40, to augment potency. Complementarity Determining Region (CDR): A region of hypervariable amino acid sequence that defines the binding affinity and specificity of an antibody. The light and heavy chains of a mammalian immunoglobulin each have three CDRs, designated VL-CDR1, VL-CDR2, VL-CDR3 and VH-CDR1, VH- CDR2, VH-CDR3, respectively. Conservative variants: Sequence variants that include conservative amino acid substitutions. Conservative amino acid substitutions are substitutions that do not substantially affect or decrease the function of a protein, for example, the ability of a protein to interact with or bind a target protein (for example, sequence variants of a GRP78 CAR that retain binding specificity for GRP78). For example, a GRP78-specific CAR can include up to 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 conservative substitutions relative to a reference sequence (e.g., SEQ ID NO: 8) and retain specific binding activity for GRP78. The following six groups are examples of amino acids that are generally considered to be conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W). Non-conservative substitutions are those that reduce an activity or function of the protein, for example, the ability to specifically bind to GRP78. Contacting: Placing an agent in direct physical association; including both in solid or liquid form. Contacting includes contacting a cell, for example, a cancerous cell, by placing an agent in direct physical association with the cell. Contacting can occur in vivo or in vitro. Control: A reference standard. A control can be a positive or negative control. In some examples, the control is a measurement from the subject prior to treatment (e.g., tumor size or load). In some examples, the control is a subject not receiving treatment (e.g., vehicle) or a subject receiving an alternative treatment. In other examples, the control is a historical control or standard reference value or range of7213-109906-02values (e.g., a group of samples that represent baseline or normal values). Practitioners can readily identify suitable controls. Effective Amount: The amount of an agent (e.g., the disclosed HSP90 inhibitor, multikinase inhibitor, or GRP78 immunotherapy) that is sufficient to effect beneficial or desired results. In a therapeutic context, an effective amount is an amount sufficient to treat, reduce, and / or ameliorate the signs or symptoms of a disease or pathological condition (e.g., cancer) in a subject. In a non-limiting example, an effective amount is an amount sufficient to inhibit or reduce tumor growth in a subject. Expression Cassette: A nucleic acid fragment designed for expression of a particular gene (or genes) in a host cell. Expression cassettes can be included in expression vectors. Glucose Regulated Protein 78 (GRP78): Also known as binding immunoglobulin protein (BIP) or heat shock protein family A member 5 (HSPA5), GRP78 is an endoplasmic reticulum (ER)-resident molecular chaperone that participates in protein processing and regulates the unfolded protein response (UPR) in the ER. UPR is a multimolecular pathway that mitigates proteotoxicity induced by misfolded proteins. In response to cellular stress, GRP78 can translocate to the plasma membrane (sometimes referred to as “cell surface GRP78”), where it can activate multiple signal transduction pathways. In cancerous cells, cell surface GRP78 is associated with increased proliferative ability, improved survival, and augmented invasive and metastatic potential. GRP78 sequence information has been described and is publicly available (see, e.g., NCBI Gene ID No: 3309; ncbi.nlm.nih.gov / gene / 3309). GRP78 Immunotherapy: An immunotherapy that targets GRP78. In some examples, the immunotherapy kills cells that express cell surface GRP78, for example, a cancer / tumor cell that expresses cell surface GRP78. Heat Shock Protein 90 (HSP90): A molecular chaperone that aids in proper folding and stabilization of specific target proteins. Some HSP90 target proteins include conditionally activated and / or expressed signaling proteins. Mutated, chimeric, or overexpressed signaling proteins can promote cancer cell growth and / or survival. HSP90 is also known as heat shock protein 90 alpha family class A member 1 (HSP90AA1). HSP90 sequence information has been described and is publicly available (see, e.g., NCBI Gene ID No: 3320; ncbi.nlm.nih.gov / gene / 3320). Heterologous: Originating from a different genetic source. A nucleic acid molecule that is heterologous to a cell is a nucleic acid that originated from a genetic source other than the cell in which it has been introduced. Since CARs are not naturally occurring, a nucleic acid encoding a CAR is heterologous to any immune cell in which it is expressed. Methods for introducing a heterologous nucleic acid molecule in a cell or organism are known, for example methods of transformation, including electroporation, lipofection, particle gun acceleration, or homologous recombination. HSP90 Inhibitor: An agent that inhibits Hsp90 function by binding HSP90 (N-terminus or C- terminus) and preventing interaction with client proteins. Exemplary HSP90 inhibitors include, but are not limited to: tanespimycin (17-AAG), luminespib (NVP-AUY922), alvespimycin (17-DMAG) HCl, ganetespib (STA-9090), BIIB021, onalespib (AT13387), geldanamycin (NSC 122750), NVP-BEP800,7213-109906-02SNX-2112 (PF-04928473), PF-04929113 (SNX-5422), KW-2478, XL888, cucurbitacin D, pseudolaric acid A, YUM70, DTHIB, rocaglamide, pimitespib (TAS-116), KRIBB11, apoptozole, VER155008, VER-50589, CH5138303, VER-49009, NMS-E973, zelavespib (PU-H71), HSP990 (NVP-HSP990), elesclomol (STA- 4783), NPX800, JG98, TRC051384, HA15, KNK437, triptolide (PG490), and DN401. HSP90 inhibition has been shown to sensitize certain cancers to chemotherapies, immune checkpoint inhibitors, and radiation therapies. Immune Cell: A cell that is part of the immune system. Immune cells develop from stem cells in the bone marrow and differentiate into different types of white blood cells. Non-limiting examples include NK cells, T cells, NKT cells, and macrophages. Immunotherapy: A therapy that uses an agent to stimulate or suppress the immune system to treat a disease, for example, cancer. Examples of cancer immunotherapy include, but are not limited to: immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, and immune system modulators. Specific, non-limiting examples include atezolizumab, avelumab, axicabtagene ciloleucel, blinotumumab, cemipilimab, durvalumab, ieramilimab, ipilimumab, nivolumab, palbociclib, pembrolizmab, pidilizumab, relatlimab, ribociclib, urelemab, utolimumab, adoptive cell transfer (ACT) therapy (e.g., chimeric antigen receptor (CAR) cells), or engineered TCR or tumor-infiltrating lymphocyte (TIL), and oncolytic viruses (e.g., talimogene laherparepvec (T-VEC)). Increase or Decrease: A positive (increase) or negative (decrease) difference relative to a control value. The difference can be a qualitative or quantitative. In some examples, the difference is statistically significant (e.g., P-Value less than 0.05 or 0.01). In some examples, the difference is an increase relative to a control of at least 5%, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 500%, or greater than 500%. In some examples, the difference is a decrease relative to a control of at least 5%, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or 100%. Isolated or Purified: An “isolated” or “purified” biological component (e.g., a nucleic acid, protein, or cell) is one that has been substantially separated from other biological components in the environment (e.g., a cell or biological sample) in which the component occurs, e.g., separated from other chromosomal and extra-chromosomal DNA and RNA, proteins and cells. Nucleic acids and proteins that have been “isolated” include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. Absolute purity or isolation is not required, it is intended as a relative term. Thus, for example, a purified / isolated protein, nucleic acid, or cell preparation is one in which the protein, nucleic acid, or cell is more enriched than the protein, nucleic acid, or cell is in its initial environment. In one example, a preparation is purified / isolated such that the protein, nucleic acid, or cell represents at least 50% of the total7213-109906-02content of the preparation. A substantially purified protein or nucleic acid is at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or at least 99% pure. Thus, in one specific, non-limiting example, a substantially purified protein or nucleic acid is 90% free of other components. Multikinase Inhibitor: A single agent that simultaneously targets and inhibits multiple kinases (e.g., VEGFRs, Raf-1, B-Raf, c-KIT) implicated in tumor growth, survival, and / or invasion. Exemplary multikinase inhibitors include: cabozantinib, imatinib, lenvatinib, regorafenib, sorafenib, sunitinib, and vandetinib. Natural Killer (NK) Cells: An immune cell that kills target cells in the absence of a specific antigenic stimulus and without restriction according to MHC class. Target cells can be tumor cells or cells harboring viruses. NK cells are characterized by the presence of CD56 and the absence of CD3 surface markers. NK cells typically comprise 10 to 15% of the mononuclear cell fraction in normal peripheral blood. Historically, NK cells were first identified by their ability to lyse certain tumor cells without prior immunization or activation. NK cells are thought to provide a “back up” protective mechanism against viruses and tumors that might escape the CTL response by down-regulating MHC class I presentation. In addition to being involved in direct cytotoxic killing, NK cells also serve a role in cytokine production (e.g., interferon-γ), which can be important to control cancer and infection. A “modified NK cell” is a non-naturally occurring NK cell that has been transformed with a heterologous nucleic acid (e.g., one or more of the nucleic acids or vectors disclosed herein) or expresses one or more heterologous proteins (e.g., a GRP78 CAR disclosed herein). The terms “modified NK cell” and “transformed NK cell” are used interchangeably. Pharmaceutically Acceptable Carrier: Includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration (see, e.g., Remington: The Science and Practice of Pharmacy, Adejare (Ed.), Academic Press, London, United Kingdom, 23rdEdition (2021)). Examples of such carriers or diluents include, but are not limited to, water, saline, Ringer’s solutions, dextrose solution, balanced salt solutions, and 5% human serum albumin. Liposomes and non-aqueous vehicles, e.g., fixed oils, may also be used. Supplementary active compounds can also be incorporated into the compositions. Actual methods for preparing administrable compositions include those provided in Remington: The Science and Practice of Pharmacy, Adejare (Ed.), Academic Press, London, United Kingdom, 23rdEdition (2021). Recombinant: A nucleic acid or protein that has a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two otherwise separated segments of sequence (e.g., a “chimeric” sequence). This artificial combination can be accomplished by chemical synthesis or by the artificial manipulation of isolated segments of nucleic acids, for example, by genetic engineering techniques. The CARs disclosed herein are recombinant proteins encoded by recombinant nucleic acids. Sequence Identity: The degree of similarity between amino acid or nucleic acid sequences. Sequence identity is frequently measured in terms of percentage identity; the higher the percentage, the more7213-109906-02similar the two sequences are. Homologs of a polypeptide (or nucleotide sequence) will possess a relatively high degree of sequence identity when aligned using standard methods. Methods of alignment of sequences for comparison have been described. The NCBI Basic Local Alignment Search Tool (BLAST) tool is often used and is available from several sources, including the National Center for Biotechnology Information (blast.ncbi.nlm.nih.gov / Blast.cgi). Various types of BLAST are available, for example, blastp, blastn, blastx, tblastn and tblastx. A description of how to determine sequence identity using this program is available on the NCBI website and other resources, for example, Altschul et al., J. Mol. Biol.215:403, 1990. In some examples, percent sequence identity is determined by using BLAST with default parameters. Single-Chain Variable Fragment (scFv): A genetically engineered molecule that contains the VH and VL domains of one or more antibody(ies) linked by a suitable polypeptide linker as a genetically fused single chain molecule. The intramolecular orientation of the VH-domain and the VL-domain in a scFv, is typically not decisive for scFvs. Thus, scFvs with both possible arrangements (VH-domain-linker domain- VL-domain; VL-domain-linker domain-VH-domain) may be used. In a dsFv the VH and VL have been mutated to introduce a disulfide bond to stabilize the association of the chains. Diabodies also are included, which are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites. Subject: A living multi-cellular vertebrate organism. In some examples, the subject is a mammal, e.g., a human, non-human primate, rat, mouse, dog, or cat. In some examples, the subject is human. T Cell: A white blood cell (lymphocyte) that is an important mediator of the immune response. T cells include, but are not limited to, CD4+T cells and CD8+T cells. A CD4+T cell is an immune cell that carries a marker on its surface known as “cluster of differentiation 4” (CD4). These cells, also known as helper T cells, help orchestrate the immune response, including antibody responses as well as killer T cell responses. CD8+T cells carry the “cluster of differentiation 8” (CD8) marker. In one implementation, a CD8+T cell is a cytotoxic T lymphocyte (CTL). Activated T cells can be detected by an increase in cell proliferation and / or expression or secretion of one or more cytokines (e.g., IL-2, IL-4, IL-6, IFN-γ, or TNFα). Activation of CD8+T cells can also be detected by an increase in cytolytic activity in response to an antigen. A natural killer T (NKT) cell is a class of T cell that expresses both T-cell receptors (TCR) characteristic of adaptive immunity, and surface receptors for NK cells, which are part of the innate immune response (e.g., the cell-surface marker NK1.1 normally associated with NK cells along with an α / β T-cell receptor) (Tupin et al. (2007) Nat Rev Microbiol 5:405–417). A “modified T cell” is a T cell transformed with a heterologous nucleic acid (e.g., one or more of the nucleic acids or vectors disclosed herein) or expressing one or more heterologous proteins (e.g., a GRP78 CAR disclosed herein). The terms “modified T cell” and “transformed T cell” are used interchangeably.7213-109906-02Similarly, a “modified NKT cell” is an NKT cell transformed with a heterologous nucleic acid (e.g., one or more of the nucleic acids or vectors disclosed herein) or expressing one or more heterologous proteins (e.g., a GRP78 CAR disclosed herein). A modified T cell or modified NKT cell is not naturally occurring. Transformed: A transformed cell is a cell into which a heterologous nucleic acid molecule has been introduced by molecular biology techniques. As used herein, the term transformation encompasses all techniques by which a nucleic acid molecule might be introduced into such a cell, including chemical methods (e.g., calcium-phosphate transfection), physical methods (e.g., electroporation, microinjection, particle bombardment), fusion (e.g., liposomes), lipofection, nucleofection, receptor-mediated endocytosis (e.g., DNA-protein complexes, viral envelope / capsid-DNA complexes), particle gun accelerator (gene gun), or transduction or transfection, for example, with viral vectors. Treating, Treatment, and Therapy: Refers to a therapeutic intervention that decreases signs or symptoms of a disease or pathological condition (e.g., cancer), including improving a subject’s physical or mental well-being, or prolonging the length of survival. Treatment may be periodically assessed by objective or subjective parameters; including the results of a physical examination, self-evaluations, blood or other clinical tests. In some examples, treating cancer includes decreasing tumor size, number, or weight (tumor burden), or increasing patient survival. Vector: A nucleic acid molecule that can be introduced into a host cell (for example, by transformation), thereby producing a transformed host cell. Recombinant DNA vectors are vectors having recombinant DNA. A vector can include nucleic acid sequences that permit it to replicate in a host cell, e.g., an origin of replication. A vector can also include one or more selectable marker genes and other genetic elements known in the art. Viral vectors are recombinant nucleic acid vectors having at least some nucleic acid sequences derived from one or more viruses. A replication deficient viral vector is a vector that requires complementation of one or more regions of the viral genome required for replication due to a deficiency in at least one replication-essential gene function. II. Overview While the use of HSP90 inhibitors is underway in several clinical trials, the high dose required for monotherapy is toxic. Here, it is shown that low to moderate doses of a HSP90 inhibitor in combination with a multikinase inhibitor improves cell killing of multikinase-resistant (MKIR)-HCC and PDAC cell lines. Secondary to cytotoxicity, it is further shown that HSP90 inhibition promotes stabilization of MICA / B on the surface of MKIR-HCC cells. Surprisingly, HSP90 inhibition in combination with regorafenib restores MICA / B on the surface of MKIR-HCC cells, reversing the effects of regorafenib and supporting NK-cell mediated killing of tumor cells. Notably, healthy hematopoietic cells did not show any changes in MICA / B expression after the HSP90 inhibitor / multikinase inhibitor combination chemotherapy. HSP90 inhibition is also shown to recover cell mediated killing of MKIR-HCC, which is reduced by regorafenib monotherapy. Two N-terminal inhibitors of HSP90 (STA-9090 and BIIB021) were tested in7213-109906-02combination with the multikinase inhibitor regorafenib and were found to have minimal cytotoxicity on expanded NK cells. The HSP90 inhibitor / multikinase inhibitor combination chemotherapy was also found to increase expression of cell surface GRP78, which could be used as an immunotherapy target. Chimeric antigen receptor (CAR)-NK therapy shows less toxicity than CAR-T therapy, and a GRP78-CAR-NK could potentially be used as an of “off-the-shelf” cell product. Moreover, the data disclosed herein suggests that HSP90 inhibition supports NK mediated killing of cancer cells. Therefore, a novel GRP78 CAR was developed for expression in NK cells to produce a GRP78 CAR-NK immunotherapy. The results disclosed herein suggest a previously unreported synergistic bridge between a combination chemotherapy (HSP90 inhibitor / multikinase inhibitor) and GRP78 immunotherapy, particularly GRP78 CAR-NK therapy. Most solid tumors show expression of cell surface GRP78, therefore this treatment strategy could be applied to numerous cancers. III. Chimeric Antigen Receptors Disclosed herein are chimeric antigen receptors (CARs), which include (a) an extracellular domain, (b) a transmembrane domain, and (c) an intracellular domain including one or more signaling domains. The CARs specifically bind GRP78. In some examples, the CARs further include a tag, e.g., an IgG1, His, or MYC tag. The CARs may also include a signal peptide, linker(s), and / or sequences for recombinant construction (e.g., one or more restriction enzyme sites). In some examples, the CARs include from N terminus to C terminus: an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain includes a binding portion that specifically binds GRP78, for example, an antibody or binding peptide specific to GRP78. In some implementations, the binding portion specific to GRP78 binds a target cell, for example, a cell expressing cell surface GRP78. In some examples, the cell is a cancer cell (including a tumor cell), for example, a lung, liver, breast, or pancreatic cancer cell. In some examples, the target is a solid tumor cell, for example, a solid tumor cell that expresses cell surface GRP78. Binding may be increased or improved by increasing or upregulating GRP78 expression in the target cell. In some examples, the binding portion is a GRP78 binding peptide (a peptide that specifically binds GRP78). In some examples, the binding portion is a GRP78 scFv (a scFv that specifically binds GRP78). In some examples, the extracellular domain includes an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1. In some examples, the extracellular domain includes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1. In some examples, the extracellular domain includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1. In a specific, non-limiting example, the extracellular domain includes SEQ ID NO: 1. In some examples, the extracellular domain includes a binding portion that consists of SEQ ID NO: 1 or a conservative variant thereof.7213-109906-02In some examples, the extracellular domain includes a tag region, for example, an IgG1, His, or MYC tag. The tag region can be used to detect CAR expression, for example, by flow cytometry. In a non- limiting example, the IgG1 tag region includes a sequence having at least 80% sequence identity to SEQ ID NO: 2, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2. In a non-limiting example, the IgG1 tag region includes a sequence having at least 90% sequence identity to SEQ ID NO: 2. In a non-limiting example, the IgG1 tag region includes a sequence having at least 95% sequence identity to SEQ ID NO: 2. In some examples, the IgG1 tag region includes or consists of SEQ ID NO: 2 or a conservative variant thereof. The transmembrane domain can mediate optimal cellular activation via dimerization of CARs and functional interaction with TCRs. Suitable transmembrane domains have been described, and include but are not limited to, transmembrane domains from: CD8, CD4, CD3ζ, CD40, OX40-L, 4-1BB, ICOS, ICOS- L, CD80, CD86, ICAM-1, LFA-1, ICAM-1, CD56, CTLA-4, PD-1, TIM-3, NKP30, NKP44, NKP40, NKP46, B7-H3, PD-L1, PD-2, and CD70. In some examples, the transmembrane domain is a CD3, CD8, or CD28 transmembrane domain. In a non-limiting example, the transmembrane domain is a CD28 transmembrane domain. In a further non-limiting example, the transmembrane domain includes an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 3, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3. In some examples, the transmembrane domain includes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 3. In some examples, the transmembrane domain includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3. In some examples, the transmembrane domain includes or consists of SEQ ID NO: 3 or a conservative variant thereof. The intracellular domain includes one or more signaling domains. Suitable signaling domains have been described, and include but are not limited to, signaling domains from: CD28, 4-1BB (CD137), CD8, CD40, OX40 (CD134), ICOS, CD27, DAP10, DAP12, OX40-L, 4-1BBL, ICOS-L, CD80, CD86, ICAM-1, LFA-1, CD56, CTLA-4, PD-1, PDK, TIM-3, NKP30, NKP44, NKP40, NKP46, B7-H3, PD-L1, PD-2, CD70, CD3ζ, and FcεRIγ. In a non-limiting example, the intracellular domain includes a signaling domain from CD28, 4-1BB, or CD3ζ. In a further non-limiting example, the one or more signaling domains include an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 4, 5, or 6, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NOS: 4, 5, or 6. In a further non-limiting example, the one or more signaling domains include an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4, 5, or 6. In a further non-limiting example, the one or more signaling domains include an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 4, 5, or 6. In some examples, the signaling domain includes or consists of SEQ ID NOS: 4, 5, and / or 6, or a conservative variant thereof. In some examples, the intracellular domain includes signaling domains from CD28, 4-1BB, and CD3ζ. In some examples, the intracellular domain includes SEQ ID NOS: 4, 5, and 6, or conservative variants thereof.7213-109906-02In some implementations, the CAR includes an amino acid sequence having at least 80% identity to SEQ ID NO: 8, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In a non-limiting example, the CAR includes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8. In a non-limiting example, the CAR includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8. In a further non-liming example, the CAR includes or consists of SEQ ID NO: 8 or a conservative variant thereof. Also provided are functional variants of the CAR or domains thereof described herein. Functional variants retain a desired biological activity (e.g., specific binding to GRP78), despite differences in amino acid sequence. The functional variant can be at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical in amino acid sequence to the parent CAR or domain. Substitutions can be made, for example, in one or more of the extracellular domain, transmembrane domain, intracellular domain, or IL-15 domain so long as the CAR remains functional (i.e., the CAR specifically binds GRP78 and facilitates killing of the target cell). In some examples, the functional variant includes at least one conservative amino acid substitution (for example, up to 10 conservative amino acid substitutions, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conservative substitutions) relative to the parent sequence. In other examples, the functional variant includes no more than 10 non-conservative amino acid substitution (for example, up to 10 non-conservative amino acid substitutions, for example, no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 non-conservative substitutions) relative to the parent sequence. For non-conservative amino acid substitutions, the substitution does not interfere with or inhibit the biological activity of the functional variant. In some examples, a non-conservative amino acid substitution may enhance the biological activity of the functional variant, such that the biological activity of the functional variant is increased as compared to the parent CAR. The CAR disclosed herein can include one or more synthetic amino acids in place of one or more naturally occurring amino acids. Such synthetic amino acids include, for example, aminocyclohexane carboxylic acid, norleucine, a-amino n-decanoic acid, homoserine, S-acetylaminomethyl-cysteine, trans-3- and trans-4-hydroxyproline, 4- aminophenylalanine, 4- nitrophenylalanine, 4-chlorophenylalanine, 4- carboxyphenylalanine, β-phenylserine β-hydroxyphenylalanine, phenylglycine, α -naphthylalanine, cyclohexylalanine, cyclohexylglycine, indoline-2-carboxylic acid, 1 ,2,3,4- tetrahydroisoquinoline-3- carboxylic acid, aminomalonic acid, aminomalonic acid monoamide, N'-benzyl-N'-methyl-lysine, Ν',Ν'- dibenzyl-lysine, 6-hydroxylysine, ornithine, α-aminocyclopentane carboxylic acid, α-aminocyclohexane carboxylic acid, oc-aminocycloheptane carboxylic acid, -(2-amino-2-norbornane)-carboxylic acid, γ- diaminobutyric acid, α,β-diaminopropionic acid, homophenylalanine, and α-tert-butylglycine. The CAR disclosed herein may be glycosylated, amidated, carboxylated, phosphorylated, esterified, N-acylated, cyclized via, e.g., a disulfide bridge, or converted into an acid addition salt and / or optionally dimerized or polymerized, or conjugated.7213-109906-02IV. Nucleic Acids, Vectors, and Cells Also provided are nucleic acids encoding CARs disclosed herein. In some examples, the nucleic acids encode an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 8, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In a specific, non-limiting example, the nucleic acid encodes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8. In a specific, non-limiting example, the nucleic acid encodes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8. In a further non-limiting example, the nucleic acid encodes SEQ ID NO: 8. In some implementations, a nucleic acid encoding a CAR disclosed herein further encodes a signal peptide. The signal peptide can be located, for example, N-terminal to the GRP78 binding portion. In some examples, the signal peptide is a Homo sapiens clone IGHV3-23_07 immunoglobulin heavy chain variable region gene signal peptide. In some implementations, a nucleic acid encoding the signal peptide includes an amino acid sequence having at least 80% identity to SEQ ID NO: 19, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 19. In a non- limiting example, the nucleic acid encoding the signal peptide encodes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 19. In a non-limiting example, the signal peptide includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 19. In a further non-liming example, the signal peptide includes or consists of SEQ ID NO: 19. In some examples, the signal peptide is encoded by a nucleic acid sequence including at least 80% identity to SEQ ID NO: 20, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 20. In a non-limiting example, a nucleic acid encoding the signal peptide includes at least 90% sequence identity to SEQ ID NO: 20. In a non-limiting example, a nucleic acid encoding the signal peptide includes at least 95% sequence identity to SEQ ID NO: 20. In a further non-liming example, a nucleic acid encoding the signal peptide includes or consists of SEQ ID NO: 20, or a degenerate variant thereof. In some implementations, the nucleic acid includes a sequence having at least 80% sequence identity to SEQ ID NO: 16, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16. In a specific, non-limiting example, the nucleic acid includes an sequence having at least 90% sequence identity to SEQ ID NO: 16. In a specific, non-limiting example, the nucleic acid includes an sequence having at least 95% sequence identity to SEQ ID NO: 16. In a further non-limiting example, the nucleic acid includes or consists of SEQ ID NO: 16 or a degenerate variant thereof. In some implementations, the nucleic acid sequence encoding a GRP78 expression cassette or construct includes one or more domains that increase survival or persistence of a host cell. In some examples, the domain is an intracellular domain from a cytokine receptor, for example, an intracellular domain from interleukin (IL)-12, IL-15, or IL-18. In some examples, the domain is located C-terminal to the CD3ζ domain of the CAR. In some implementations, the expression cassette or construct includes an intracellular IL-15 domain that improves persistence or survival of NK cells. In some examples, the7213-109906-02intracellular domain constitutively expresses and produces active IL-15. In a non-limiting example, the IL- 15 domain includes a sequence having at least 80% sequence identity to SEQ ID NO: 7, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 7. In a non-limiting example, the IL-15 domain includes a sequence having at least 90% sequence identity to SEQ ID NO: 7. In a non-limiting example, the IL-15 domain includes a sequence having at least 95% sequence identity to SEQ ID NO: 7. In some examples, the IL-15 domain includes or consists of SEQ ID NO: 7. In some implementations, the IL-15 domain is encoded by a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 15, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 15. In a specific, non-limiting example, the IL-15 domain is encoded by a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 15. In a specific, non-limiting example, the IL-15 domain is encoded by a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 15. In a further non-limiting example, the IL-15 domain is encoded by a nucleic acid sequence including or consisting of SEQ ID NO: 15 or a degenerate variant thereof. In some examples, the IL-15 domain is located C-terminal to the CD3ζ domain of the CAR. Also provided are nucleic acid sequences encoding a GRP78 expression cassette that includes (i) a GRP78 chimeric antigen receptor (CAR) and (ii) an IL-15 domain. In some examples, the GRP78 CAR includes an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1. In a specific, non-limiting example, the GRP78 CAR includes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1. In another non-limiting example, the GRP78 CAR includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1. In a further non-limiting example, the GRP78 CAR includes SEQ ID NO: 1 or a conservative variant thereof. In some implementations, the GRP78 CAR includes an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 8, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In a specific, non-limiting example, the GRP78 CAR includes an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8. In a specific, non-limiting example, the GRP78 CAR includes an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8. In a further non-limiting example, the GRP78 CAR includes or consists of SEQ ID NO: 8 or a conservative variant thereof. In some implementations, the GRP78 CAR is encoded by a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 16, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16. In a specific, non-limiting example, the GRP78 CAR is encoded by a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 16. In another non-limiting example, the GRP78 CAR is encoded by a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 16. In a further non-limiting example, the GRP78 CAR is encoded by a nucleic acid sequence including or consisting of SEQ ID NO: 16 or a degenerate variant thereof.7213-109906-02In some implementations, the GRP78 expression cassette includes a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 17, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 17. In a specific, non-limiting example, the GRP78 expression cassette includes a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 17. In another non-limiting example, the GRP78 expression cassette includes a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 17. In a further non-limiting example, the GRP78 expression cassette includes or consists of SEQ ID NO: 17 or a degenerate variant thereof. In some implementations, the GRP78 expression cassette includes a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 18, for example, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 18. In a specific, non-limiting example, the GRP78 expression cassette includes a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 18. In another non-limiting example, the GRP78 expression cassette includes a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 18. In a further non-limiting example, the GRP78 expression cassette includes or consists of SEQ ID NO: 18 or a degenerate variant thereof. In some examples, the nucleic acid sequence encoding the GRP78 expression cassette is included on a vector, for example, a vector disclosed herein. In some implementations, the disclosed nucleic acid sequences (e.g., nucleic acids encoding the CAR or GRP78 expression cassette disclosed herein) are degenerate variants of a particular reference sequence (for example, any of SEQ ID NOs: 9-18). Degenerate variants are nucleic acid sequence variants that encode the same amino acid sequence. Degenerate variants occur due to degeneracy (i.e., redundancy) of the genetic code, whereby more than one codon can encode the same amino acid residue. Thus, for example, leucine can be encoded by CTT, CTC, CTA, CTG, TTA, or TTG; serine can be encoded by TCT, TCC, TCA, TCG, AGT, or AGC; asparagine can be encoded by AAT or AAC; aspartic acid can be encoded by GAT or GAC; cysteine can be encoded by TGT or TGC; alanine can be encoded by GCT, GCC, GCA, or GCG; glutamine can be encoded by CAA or CAG; tyrosine can be encoded by TAT or TAC; isoleucine can be encoded by ATT, ATC, or ATA; etc. The disclosed nucleic acid sequences (e.g., nucleic acids encoding the CAR or GRP78 expression cassette disclosed herein) can be codon optimized for expression in a particular host cell, for example, human, mouse, or bacteria. Codon preferences and codon usage tables for a particular species can be used to engineer isolated nucleic acid molecules encoding protein products, for example, a CAR disclosed herein, that take advantage of the codon usage preferences of a particular species. In some examples, the nucleic acids are codon optimized for expression in human. In some examples, the nucleic acids are codon optimized for a particular protein expression system, for example, bacteria, yeast, insect, or CHO expression systems. The disclosed nucleic acids (e.g., nucleic acids encoding the CAR or GRP78 expression cassette disclosed herein) can be prepared using any suitable method, including standard molecule cloning techniques or direct chemical synthesis. In some examples, the disclosed nucleic acids are prepared by7213-109906-02molecular cloning or amplification methods. Amplification methods include the polymerase chain reaction (PCR), the ligase chain reaction (LCR), the transcription-based amplification system (TAS), the self- sustained sequence replication system (3SR), and the Qβ replicase amplification system (QB). A wide variety of cloning and in vitro amplification methodologies have been previously described. Suitable molecular cloning and amplification techniques have been described, for example, in Green and Sambrook (Molecular Cloning: A Laboratory Manual, 4thed., New York: Cold Spring Harbor Laboratory Press, 2012) and Ausubel et al. (Eds.) (Current Protocols in Molecular Biology, New York: John Wiley and Sons, including supplements). In some examples, the disclosed nucleic acids (e.g., nucleic acids encoding the CAR or GRP78 expression cassette disclosed herein) are prepared by direct chemical synthesis. Many methods of chemical synthesis have been described, for example, the phosphotriester method of Narang et al., Meth. Enzymol. 68:90-99, 1979; the phosphodiester method of Brown et al., Meth. Enzymol.68:109-151, 1979; the diethylphosphoramidite method of Beaucage et al., Tetra. Lett.22:1859-1862, 1981; the solid phase phosphoramidite triester method described by Beaucage & Caruthers, Tetra. Letts.22(20):1859-1862, 1981, for example, using an automated synthesizer as described in, for example, Needham-VanDevanter et al., Nucl. Acids Res.12:6159-6168, 1984; and, the solid support method of U.S. Patent No.4,458,066. Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence, or by polymerization with a DNA polymerase using the single strand as a template. Also provided are vectors (e.g., plasmids, viral vectors, cosmids, artificial chromosomes) encoding a nucleic acid disclosed herein (e.g., a nucleic acid encoding the CAR or GRP78 expression cassette disclosed herein). Certain vectors are capable of directing the expression of genes to which they are operatively- linked. Such vectors are sometimes referred to as “expression vectors.” In some implementations, a nucleic acid molecule encoding a disclosed CAR or GRP78 expression cassette is included on a vector (for example, a viral vector) for expression in a host cell, for example, an immune cell (e.g., T cell, NK cell, NKT cell, or macrophage). One type of vector is a “plasmid,” which refers to a circular double stranded DNA loop into which additional DNA segments can be inserted, for example, by standard molecular cloning techniques. Another type of vector is a viral vector, wherein virally-derived DNA or RNA sequences are present in the vector for packaging into a virus (e.g., retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses). A replication deficient viral vector is a vector that requires complementation of one or more regions of the viral genome required for replication due to a deficiency in at least one replication-essential gene function. In some examples, the vector is a viral vector, for example, a retrovirus (e.g., MoMLV or lentivirus) or adeno-associated viral (AAV) vector. Other suitable viral vectors include polyoma, SV40, vaccinia virus, herpes viruses including HSV and EBV, Sindbis viruses, alphaviruses and retroviruses of avian, murine, and human origin, baculovirus (Autographa californica multinuclear polyhedrosis virus; AcMNPV) vectors,7213-109906-02retrovirus vectors, polio vectors, orthopox vectors, avipox vectors, fowlpox vectors, capripox vectors, suipox vectors, adenoviral vectors, herpes virus vectors, alpha virus vectors, baculovirus vectors, Sindbis virus vectors, vaccinia virus vectors and poliovirus vectors. Specific exemplary pox viruses of use include orthopox, suipox, avipox, and capripox virus. Orthopox includes vaccinia, ectromelia, and raccoon pox. One example of an orthopox of use is vaccinia. Avipox includes fowlpox, canary pox and pigeon pox. Capripox includes goatpox and sheeppox. In one example, the suipox is swinepox. Vectors can include one or more regulatory elements (e.g., promoter (for example, CMV, SV40, EF1α, β-actin, hPGK, or RPBSA); transcription start site (TSS); enhancers; insulators; A / T-rich regions; transcription factor (TF) binding sites; transcription and / or translation terminators; initiation sequences, or other regulatory element), which may be selected on the basis of the host cell to be used for expression, that is operably-linked to the nucleic acid sequence to be expressed. "Operably linked" means that the nucleotide sequence of interest is linked to the regulatory element(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription / translation system or in a host cell when the vector is introduced into the host cell). Vector expression can be constitutive (e.g., SV40, CMV, UBC, EF1α, PGK, and CAGG), inducible (e.g., IPTG), or cell / tissue specific (for example, T cell specific, e.g., dLck or CD3δ). In some examples, the promoter is a synthetic promoter that is inducible upon CAR cell activation (e.g., “iSynPro” promoters, see, WO 2018 / 213332). A vector can be introduced into a host cell to express a product encoded by a nucleic acid described herein (e.g., a CAR disclosed herein). A vector can also include one or more selectable marker genes, for example, an antibiotic (e.g., puromycin, hygromycin), or a detectable marker (e.g., GFP, YFP, RFP, luciferase, X-gal). In some examples, a selectable marker or reporter is not included in the vector. In some implementations, the CAR expression cassette or vector further include an inducible gene (e.g., inducible caspase 9 (iCasp9) or inducible proapoptotic molecule) or an inducible activation system (e.g., My88 / CD40 (iMC) that can be used to eliminate cells expressing the CAR (e.g., a “suicide” gene or “safety switch”). The inducible gene / activation system can be activated in the event of off target side effects (or on target / off tumor effects), for example, cytokine release syndrome (“cytokine storm”). Safety switch systems have been described, for example, in Gargett and Brown (2014) Front. Pharmacol.5: 235, and Gerken et al. (2017) Cancer Discov.7(11): 1306-1319. In some examples, the vector encoding the safety switch is a different vector than the vector encoding a CAR (including encoding a GRP78 expression cassette) disclosed herein. In some examples, the vector encoding the safety switch also encodes a CAR disclosed herein. In some examples, activation of the safety switch eliminates cells transformed with a CAR disclosed herein, for example, by eliminating at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% at least 99%, or 100% of the transformed cells. Also provided are host cells that include a CAR, nucleic acid, or vector disclosed herein. The host cell can be prokaryotic (e.g., bacteria) or eukaryotic (e.g., human). In some implementations, the host cell is a cell type suitable for protein expression and / or production of viruses. Exemplary cell types include7213-109906-02microbial (e.g., bacterial or yeast), archaea, insect, fungi, plant, or mammalian cells. Non-limiting examples of specific cell lines include Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Salmonella typhimurium, SF9 cells, C129 cells, 293 cells, Neurospora, and immortalized mammalian myeloid and lymphoid cell lines. Non-limiting examples of commonly used mammalian host cell lines include VERO and HeLa, HEK 293T (293T), CHO, WI38, BHK, and COS cell lines, however, other cell lines may be used, for example, cells designed to provide higher expression, or desirable post-translational modifications (e.g., glycosylation patterns), or other features. In some examples, a nucleic acid or vector disclosed herein (e.g., nucleic acids or vectors encoding the CAR disclosed herein) is codon optimized for expression in a particular organism, for example, in a bacterium (e.g., E. coli), fungi (e.g., S. cerevisiae), plant (e.g., N. tabacum NT-1), or animal (e.g., human HEK 293T cells, T cells, or NK cells). In some implementations, the host cell is a 293T cell. In some implementations, the host cell is an immune cell (e.g., a mammalian immune cell, including a human immune cell). Exemplary immune cells include T cells, NK cells, NKT cells, and / or macrophages. In some examples, the host cell is a NK cell (e.g., a mammalian NK cell, including a human NK cell). The immune cells can be isolated immune cells, for example, isolated T cells, isolated NK cells, isolated NKT cells, or isolated macrophages. Isolated cells can be obtained from a subject, for example, a healthy donor or a subject having cancer. In some examples, the immune cells are isolated from peripheral blood, lymph node, thymus, bone marrow, tumor tissue, adipose tissue, human embryonic stem cells (hESC), induced pluripotent stem cells (iPSC), or umbilical cord blood, of a subject. In a non-limiting example, the cells are NK cells isolated from peripheral blood of a subject. Cell types can be identified based on the presence or absence of expression markers, for example, NK cells are CD56 positive and CD3 negative, T cells can be CD4 or CD8 positive, NKT cells are NK1.1 positive and α / β T-cell receptor positive, and macrophages express a number or receptors, including PRRs, TLRs, C-type lectin receptors, scavenger receptors, RLRs, and NOD-like receptors. In some examples, the cells are isolated NK cells. In some examples, the NK cells are CD56+CD3- NK cells derived from Peripheral Blood Mononuclear Cells (PBMC) or Cord Blood. NK cells can be isolated using a lymphocyte isolation kit. In some examples, the NK cells are GRP78 negative. In some implementations, immune cells obtained from a subject are enriched, purified, and / or expanded, before and / or after transformation with a vector or nucleic acid disclosed herein. In some examples, the immune cells (e.g., T cell, NK cell, NKT cell, or macrophage), are harvested and expanded from a subject with cancer. In some examples, the immune cells (e.g., T cell, NK cell, NKT cell, or macrophage), are harvested and expanded from a subject without cancer. In some implementations, the host cell is transformed with a nucleic acid encoding a CAR disclosed herein, or a vector encoding the nucleic acid. Exemplary methods of transforming cells (e.g., immune cells) include chemical transformation (calcium phosphate), electroporation, microinjection, heat shock, lipofection, and particle bombardment. In some examples, the nucleic acid or vector is introduced by contacting the cells with a nanoparticle including the nucleic acid or vector. Transformation can be used for stable or transient expression. Following transformation, cells expressing the CAR can be detected and / or7213-109906-02enriched, for example, by flow cytometry. In some examples, transformed cells (for example, T cells, NK cells, NKT cells, or macrophages) are expanded, for example, by cell culture for a period of time following transformation. In some examples, some or all of the transformed immune cells are cryopreserved for later use. In some implementations, the host cell expresses a CAR having at least 80% identity to SEQ ID NO: 8, for example, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO: 8. In some examples, the host cell expresses a CAR having at least 90% identity to SEQ ID NO: 8. In some examples, the host cell expresses a CAR having at least 95% identity to SEQ ID NO: 8. In some examples, the host cell express a CAR including or consisting of SEQ ID NO: 8 or a conservative variant thereof. In some implementations, the host cell is transformed with a nucleic acid sequence having at least 80% identity to SEQ ID NO: 16, for example, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO: 16. In some examples, the host cell is transformed with a nucleic acid sequence having at least 90% identity to SEQ ID NO: 16. In some examples, the host cell is transformed with a nucleic acid sequence having at least 95% identity to SEQ ID NO: 16. In some examples, the host cell is transformed with a nucleic acid sequence that includes or consists of SEQ ID NO: 16 or a degenerate variant thereof. In some implementations, the host cell is transformed with a nucleic acid sequence having at least 80% identity to SEQ ID NO: 17, for example, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO: 17. In some examples, the host cell is transformed with a nucleic acid sequence having at least 90% identity to SEQ ID NO: 17. In some examples, the host cell is transformed with a nucleic acid sequence having at least 95% identity to SEQ ID NO: 17. In some examples, the host cell is transformed with a nucleic acid sequence that includes or consists of SEQ ID NO: 17 or a degenerate variant thereof. In some implementations, the host cell is transformed with a nucleic acid sequence having at least 80% identity to SEQ ID NO: 18, for example, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO: 18. In some examples, the host cell is transformed with a nucleic acid sequence having at least 90% identity to SEQ ID NO: 18. In some examples, the host cell is transformed with a nucleic acid sequence having at least 95% identity to SEQ ID NO: 18. In some examples, the host cell is transformed with a nucleic acid sequence that includes or consists of SEQ ID NO: 18 or a degenerate variant thereof. Also disclosed are pharmaceutical compositions that include a CAR disclosed herein, a host cell expressing the CAR, or a nucleic acid molecule or vector a nucleic acid disclosed herein (e.g., a nucleic acid encoding the CAR or GRP78 expression cassette), in a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for treating cancer, for example, a cancer that expresses GRP78. In some examples, the cancer is a solid tumor, for example, lung, liver, breast, or pancreatic cancer. The pharmaceutical composition can be a solution of a CAR disclosed herein, a host cell expressing the CAR, or a nucleic acid molecule or vector encoding the CAR or GRP78 expression cassette, dissolved in a pharmaceutically acceptable carrier, for example, an aqueous carrier. A variety of aqueous carriers can be7213-109906-02used, for example, buffered saline and the like. These solutions are sterile and generally free of undesirable matter. These compositions may be sterilized by any suitable technique. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, for example, pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of antibody in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight and the like in accordance with the particular mode of administration selected and the subject’s needs. Any suitable method may be used for preparing administrable compositions; non-limiting examples are provided publications, for example, Remington: The Science and Practice of Pharmacy, Adejare (Ed.), Academic Press, London, United Kingdom, 23rdEdition (2021). The pharmaceutical composition can be administered by any suitable route and can be formulated for systemic or local administration. In one example, the pharmaceutical composition is formulated for parenteral administration, for example, intravenous or intratumoral administration. In some examples, the pharmaceutical composition is formulated for administration by slow infusion, rather than in an intravenous push or bolus. In another example, the pharmaceutical composition is formulated for administration by an osmotic pump (e.g., an Alzet pump) or mini-pump (e.g., an Alzet mini-osmotic pump), which allows for controlled, continuous and / or slow-release delivery of the pharmaceutical composition over a pre- determined period. The osmotic pump or mini-pump can be implanted subcutaneously, or near a target site. The pharmaceutical composition can be prepared in unit dosage form, for example, in a kit, for administration to a subject. V. Methods of Treatment Also disclosed are methods of treating cancer in a subject, including administering an effective amount of a GRP78 immunotherapy, such as immune cells (e.g., T cells, NK cells, NKT cells, or macrophages) expressing a GRP78 CAR (e.g., a GRP78 CAR disclosed herein) to the subject. In some examples, a subject that has, or is suspected of having, a cancer that expresses GRP78 is selected for treatment. The immune cells can be immune cells isolated from a sample, for example, a peripheral blood sample of a subject, that are subsequently transformed with a nucleic acid encoding the CAR (including a GRP78 expression cassette) disclosed herein. In some examples, the immune cells are autologous to the subject (from the subject). In other examples, the immune cells are allogeneic (from a donor). In some examples, the sample is from a subject that has cancer. In some examples, the immune cells are enriched, purified, and / or expanded after isolation from the sample and / or after transformation with a nucleic acid or vector (e.g., a nucleic acid or vector disclosed herein encoding a GRP78 CAR or expression cassette). In some implementations, the methods include administering to a subject a composition including immune cells expressing the GRP78 CAR and a pharmaceutically acceptable carrier. Also disclosed are methods of treating a subject with cancer, including administering a HSP90 inhibitor, a multikinase inhibitor, and a GRP78 immunotherapy to the subject, thereby treating the cancer.7213-109906-02In some examples, a therapeutically effective amount is administered to the subject, for example, an amount that reduces any sign or symptom of cancer (for example, tumor size or number of tumors). In some implementations, the HSP90 inhibitor and multikinase inhibitor are administered as a first step, and the GRP78 immunotherapy is administered as a second step, for example, to allow the HSP90 inhibitor and multikinase inhibitor prime the target cancer for GRP78 immunotherapy. In some implementations, the GRP78 immunotherapy is administered within 12 hours to 7 days after administration of the HSP90 inhibitor and multikinase inhibitor, for example, 12 hours to 6 days, 12 hours to 5 days, 12 hours to 4 days, 12 hours to 3 days, 12 hours to 2 days, 12 hours to 48 hours, 12 hours to 36 hours, 12 hours to 24 hours, 12 hours to 18 hours, 18 hours to 7 days, 18 hours to 6 days, 18 hours to 5 days, 18 hours to 4 days, 18 hours to 3 days, 18 hours to 2 days, 18 hours to 48 hours, 18 hours to 36 hours, 18 hours to 24 hours, 24 hours to 7 days, 24 hours to 6 days, 24 hours to 5 days, 24 hours to 4 days, 24 hours to 3 days, 24 hours to 2 days, 24 hours to 48 hours, 24 hours to 36 hours, 36 hours to 7 days, 36 hours to 6 days, 36 hours to 5 days, 36 hours to 4 days, 36 hours to 3 days, 36 hours to 2 days, 36 hours to 48 hours, 48 hours to 7 days, 48 hours to 6 days, 48 hours to 5 days, 48 hours to 4 days, 48 hours to 3 days, 2 days to 7 days, 2 days to 6 days, 2 days to 5 days, 2 days to 4 days, 2 days to 3 days, 3 days to 7 days, 3 days to 6 days, or 3 days to 5 days. In a non- limiting example, the GRP78 immunotherapy is administered within 18 to 48 hours after administration of the HSP90 inhibitor and multikinase inhibitor. In some implementations, the GRP78 immunotherapy is administered about 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 2 days, 3 days, 4 days, 5 days, or 6 days after administration of the HSP90 inhibitor and multikinase inhibitor. In a non-limiting example, the GRP78 immunotherapy is administered about 24 hours after administration of the HSP90 inhibitor and multikinase inhibitor. In some examples, the methods include i) detecting cell surface GRP78 expression in a cancer cell from the subject and ii) administering a HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy. In some examples, the HSP90 inhibitor and multikinase inhibitor are administered to the subject, cell surface expression of GRP78 is detected in a cancer cell of the subject, and then the GRP78 immunotherapy is administered to the subject. In some examples, the HSP90 inhibitor, multikinase inhibitor, and GRP immunotherapy are administered simultaneously or substantially simultaneously. In some examples, the HSP90 inhibitor and multikinase inhibitor are administered as adjuvant chemotherapy for 72 hours, followed by administration of the GRP78 immunotherapy (e.g., a GRP78 CAR-NK cells). In some examples, treatment is repeated, for example, at least 2, 3, 4, 5, 6 times or more. The GRP78 immunotherapy (e.g., GRP78 CAR-NK cells) can be administered before or after the HSP90 inhibitor and multikinase inhibitor. In some examples, a GRP78 immunotherapy (e.g., GRP78 CAR-NK cells) is administered after the HSP90 inhibitor and multikinase inhibitor adjuvant chemotherapy (for example, when there is low-GRP78 expression on tumor cells prior to beginning treatment). In some implementations, the effective amount of the HSP90 inhibitor and / or multikinase inhibitor is an amount that increases expression of cell surface GRP78 on a target cancer cell relative to a control (for example, cell surface expression of GRP78 prior to treatment with the HSP90 inhibitor and / or multikinase7213-109906-02inhibitor), and / or targets and kills cancerous cells or increases survival of the subject. In some examples, administering the HSP90 inhibitor and / or multikinase inhibitor increases cell surface GRP78 expression of cancer cells by at least 5% relative to a control (e.g., GRP78 expression prior to administering the HSP90 inhibitor and / or multikinase inhibitor), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 500%, or more relative to a control. In some examples, administering the HSP90 inhibitor and / or multikinase inhibitor increases cell surface GRP78 expression of cancer cells by at least 50% relative to a control. In some examples, administering the HSP90 inhibitor and / or multikinase inhibitor increases cell surface GRP78 expression of cancer cells by at least 100% relative to a control. In some implementations, the effective amount of the GRP78 immunotherapy is an amount that kills target cancer cells and / or increases survival of the subject. In some examples, administering the GRP78 immunotherapy kills at least 5% of cancer cells relative to a control (e.g., subjects not receiving the GRP78 immunotherapy), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% relative to a control. In some examples, administering the GRP78 immunotherapy increases survival of the subject by at least 5% relative to a control (e.g., subjects not receiving the GRP78 immunotherapy), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 500%, or more relative to a control. In some examples, administering the GRP78 immunotherapy increases survival by at least 10% relative to a control. In some examples, administering the GRP78 immunotherapy increases survival by at least 20% relative to a control. In some implementations, an effective amount of the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy is an amount that decreases tumor weight, volume, or metastasis, or increases survival of the subject. In some examples, administering the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy decreases tumor weight, volume, or metastasis by at least 5% relative to a control (e.g., a measurement prior to administering the combination chemotherapy and immunotherapy), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% relative to a control. In some examples, administering the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy increases cancer survival by at least 5% relative to a control (e.g., subjects not receiving the combination chemotherapy and immunotherapy), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 500%, or more relative to a control. In some examples, administering the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy increases survival of the subject by at least 5% relative to a control (e.g., subjects not receiving the chemotherapy-immunotherapy combination treatment), for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at7213-109906-02least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 500%, or more relative to a control. In some examples, administering the GRP78 immunotherapy increases survival by at least 10% relative to a control. In some examples, administering the GRP78 immunotherapy increases survival by at least 20% relative to a control. In some examples, the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy have a synergistic effect on treating the cancer. In some implementations, the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy are included in a pharmaceutical composition, which includes a pharmaceutically acceptable carrier. In some implementations, the methods include administering one or more pharmaceutical compositions including the HSP90 inhibitor, multikinase inhibitor, and GRP78 immunotherapy, for example, administering a pharmaceutical composition including the HSP90 inhibitor, administering a pharmaceutical composition including the multikinase inhibitor, and administering a pharmaceutical composition including the GRP78 immunotherapy. In some examples, the HSP90 inhibitor and the multikinase inhibitor are formulated in the same pharmaceutical composition. In some examples, the HSP90 inhibitor, the multikinase inhibitor, and the GRP78 immunotherapy are formulated as separate pharmaceutical compositions. Such pharmaceutical compositions are useful for treating cancer, for example, cancer that expresses cell surface GRP78. In some implementations, the GRP78 immunotherapy includes adoptive cell therapy, for example, tumor infiltrating lymphocyte (TIL), engineered T cell receptor (TCR), or chimeric antigen receptor (CAR) that specifically targets GRP78. In some examples the TIL is a non-naturally occurring TIL. In some examples, the immunotherapy includes a CAR, and the CAR includes a sequence that has at least 80% sequence identity to SEQ ID NO: 1, for example, at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity to SEQ ID NO: 1, and specifically binds GRP78. In a specific, non-limiting example, the immunotherapy includes a CAR that has at least 90% sequence identity to SEQ ID NO: 1 and specifically binds GRP78. In a specific, non-limiting example, the immunotherapy includes a CAR that has at least 95% sequence identity to SEQ ID NO: 1 and specifically binds GRP78. In a further non-limiting example, the immunotherapy includes a CAR that includes SEQ ID NO: 1 or a conservative variant thereof. In some examples, the immunotherapy includes a CAR, and the CAR includes a sequence that has at least 80% sequence identity to SEQ ID NO: 8, for example, at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity to SEQ ID NO: 8, and specifically binds GRP78. In a specific, non-limiting example, the immunotherapy includes a CAR that has at least 90% sequence identity to SEQ ID NO: 8 and specifically binds GRP78. In a specific, non-limiting example, the immunotherapy includes a CAR that has at least 95% sequence identity to SEQ ID NO: 8 and specifically binds GRP78. In a further non-limiting example, the immunotherapy includes a CAR that includes or consists of SEQ ID NO: 8 or a conservative variant thereof. In some examples, the CAR is expressed in an immune cell, for example, a NK cell, T cell, NKT cell, or macrophage. In some examples, the CAR is expressed in an NK cell.7213-109906-02In some examples, the GRP78 immunotherapy is GRP78-CAR T cell, for example, a GRP78-CAR T cell described in Hebbar et al. “CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells” Nat Commun.13(1):587, 2022; or Ibanez et al. “GRP78-CAR T cell effector function against solid and brain tumors is controlled by GRP78 expression on T cells” Cell Rep Med.4(11):101297, 2023. In some examples, the GRP78 immunotherapy is a nanobody, for example nanobody V80 as described in Aghamollaei et al. “Isolation and characterization of a novel nanobody for detection of GRP78 expressing cancer cells” Biotechnology and Applied Biochemistry 68(2): 239-246, 2021. In some implementations, the HSP90 inhibitor includes one or more of: tanespimycin (17-AAG), luminespib (NVP-AUY922), alvespimycin (17-DMAG) HCl, ganetespib (STA-9090), BIIB021, onalespib (AT13387), geldanamycin (NSC 122750), NVP-BEP800, SNX-2112 (PF-04928473), PF-04929113 (SNX- 5422), KW-2478, XL888, cucurbitacin D, pseudolaric acid A, YUM70, DTHIB, rocaglamide, pimitespib (TAS-116), KRIBB11, apoptozole, VER155008, VER-50589, CH5138303, VER-49009, NMS-E973, zelavespib (PU-H71), HSP990 (NVP-HSP990), elesclomol (STA-4783), NPX800, JG98, TRC051384, HA15, KNK437, triptolide (PG490), and DN401. In some implementations, the HSP90 inhibitor includes STA-9090, BIIB021, 17-AAG, or SNX-2112. In some implementations, the HSP90 inhibitor includes STA- 9090 and BIIB021. In some examples, the HSP90 inhibitor includes or consists of STA-9090. In some examples, the HSP90 inhibitor includes or consists of BIIB021. In some implementations, that multikinase inhibitor includes one or more of: cabozantinib, imatinib, lenvatinib, regorafenib, sorafenib, sunitinib, and vandetinib. In some examples, the multikinase inhibitor includes regorafenib, sorafenib, or lenvatinib. In some examples, the multikinase inhibitor includes regorafenib and sorafenib. In some examples, the multikinase inhibitor includes or consists of regorafenib. In some examples, the HSP90 inhibitor is STA-9090 or BIIB021, the multikinase inhibitor is regorafenib or sorafenib, and the GRP78 immunotherapy includes a CAR that specifically binds GRP78, for example, a CAR disclosed herein. In a further example, the HSP90 inhibitor is STA-9090, the multikinase inhibitor is regorafenib, and the GRP78 immunotherapy is a CAR that specifically binds GRP78, for example, a CAR disclosed herein. In some examples, the HSP90 inhibitor is STA-9090, the multikinase inhibitor is regorafenib, and the GRP78 immunotherapy is a GRP78 CAR-NK cell, for example, NK cells expressing a CAR disclosed herein. Any of the methods disclosed herein can include a step of selecting a subject having cancer for treatment. In some implementations, the methods disclosed herein include selecting a subject having a solid tumor for treatment. In some examples, the subject has a solid tumor, for example, the patient has lung, liver, breast, or pancreatic cancer. In some implementations, the methods disclosed herein include selecting a subject having a tumor that expresses cell surface GRP78 for treatment. In some implementations, the methods disclosed herein include a first step of detecting cell surface GRP78 expression of the cancer, and / or a step of detecting cell surface GRP78 expression after administering the HSP90 inhibitor. Expression of cell surface GRP78 can be detected, for example, by obtaining a sample of tumor cells from7213-109906-02the subject and performing flow cytometry with labeled antibodies that bind GRP78 and / or immunohistochemically staining for GRP78 using one or more polyclonal antibodies. In some implementations, the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy, is included in a pharmaceutical composition that includes a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration (see, e.g., Remington: The Science and Practice of Pharmacy, Adejare (Ed.), Academic Press, London, United Kingdom, 23rdEdition (2021)). Examples of such carriers or diluents include, but are not limited to, water, saline, Ringer’s solutions, dextrose solution, balanced salt solutions, and 5% human serum albumin. Liposomes and non-aqueous vehicles, for example, fixed oils may also be used. Supplementary active compounds can also be incorporated into the compositions. Actual methods for preparing administrable compositions include those provided in Remington: The Science and Practice of Pharmacy, Adejare (Ed.), Academic Press, London, United Kingdom, 23rdEdition (2021). In some implementations, the GRP78 immunotherapy is a CAR-NK cell that specifically binds GRP78 (for example, a GRP78 CAR-NK cell disclosed herein). In some examples, about 104to 1012CAR- NK cells are administered to the subject, for example, 104-108, 106-107, 106-108, 106-1010, 106-1012, 108-1010, or 108-1012CAR-NK cells. In some examples, about 106to 108cells per kg (of the subject’s weight) are administered to the subject. In some examples, about 107to 108cells per kg (of the subject’s weight) are administered to the subject. In some examples, at least 104, 105, 106, 107, or 108CAR-NK cells are administered to the subject. In further examples, no more than 104, 105, 106, 107108, 109, or 1010CAR-NK cells are administered to the subject. In some examples, about 104to 1010CAR-NK cells / kg, for example, about 104, 105, 106, 107, 108, 109, or 1010cells / kg, are administered to the subject. Multiple doses of the population of CAR-NK cells can be administered to a subject. For example, CAR-NK cells can be administered daily, every other day, twice per week, weekly, every other week, every three weeks, monthly, or less frequently. The dosage and frequency of administration can be affected by a number of factors, for example, the condition being treated, severity of symptoms, the subject’s age or overall condition, etc. Typically, treatment regimens are determined by clinical trials. Any suitable route of administration can be used to administer the CAR-NK cells. CAR-NK cells are typically administered parenterally, for example intravenously; however, injection or infusion in close proximity to a target tumor (e.g., local administration) or administration to the peritoneal cavity can also be used. Appropriate routes of administration can be determined by a practitioner based on factors, for example, the condition being treated, severity of symptoms, the subject’s age or overall condition, or other factors. In some implementations, the methods include administering the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy to the subject. Suitable doses of the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy may vary depending on a number of factors, however, exemplary dosages range from about 0.001 mg to about 100 mg per kg body weight of the subject, for example, about7213-109906-020.01 mg / kg to about 100 mg / kg, about 0.1 to about 100 mg / kg, about 0.5 mg / kg to about 100 mg / kg, about 1 mg / kg to about 100 mg / kg, about 5 mg / kg to about 100 mg / kg, about 10 mg / kg to about 100 mg / kg, about 15 mg / kg to about 100 mg / kg, about 20 mg / kg to about 100 mg / kg, about 25 mg / kg to about 100 mg / kg, about 30 mg / kg to about 100 mg / kg, about 35 mg / kg to about 100 mg / kg, about 40 mg / kg to about 100 mg / kg, about 45 mg / kg to about 100 mg / kg, about 50 mg / kg to about 100 mg / kg, about 55 mg / kg to about 100 mg / kg, about 60 mg / kg to about 100 mg / kg, about 65 mg / kg to about 100 mg / kg, about 70 mg / kg to about 100 mg / kg, about 75 mg / kg to about 100 mg / kg, about 80 mg / kg to about 100 mg / kg, about 85 mg / kg to about 100 mg / kg, about 90 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 50 mg / kg, about 0.5 mg / kg to about 50 mg / kg, about 1 mg / kg to about 50 mg / kg, about 5 mg / kg to about 50 mg / kg, about 10 mg / kg to about 50 mg / kg, about 15 mg / kg to about 50 mg / kg, about 20 mg / kg to about 50 mg / kg, about 25 mg / kg to about 50 mg / kg, about 30 mg / kg to about 50 mg / kg, about 35 mg / kg to about 50 mg / kg, about 40 mg / kg to about 50 mg / kg, about 0.01 mg / kg to about 20 mg / kg, about 0.5 mg / kg to about 20 mg / kg, about 1 mg / kg to about 20 mg / kg, about 5 mg / kg to about 20 mg / kg, about 10 mg / kg to about 20 mg / kg, about 15 mg / kg to about 20 mg / kg, about 0.001 mg / kg to about 1 mg / kg, about 0.01 mg / kg to about 1 mg / kg, about 0.1 mg / kg to about 1 mg / kg, about 0.25 mg / kg to about 1 mg / kg, about 0.5 mg / kg to about 1 mg / kg, about 0.001 mg / kg to about 5 mg / kg, about 0.01 mg / kg to about 5 mg / kg, about 0.1 mg / kg to about 5 mg / kg, about 0.25 mg / kg to about 5 mg / kg, about 0.5 mg / kg to about 5 mg / kg, about 1 mg / kg to about 5 mg / kg, about 0.001 mg / kg to about 10 mg / kg, about 0.01 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.5 mg / kg to about 10 mg / kg, about 1 mg / kg to about 10 mg / kg, about 5 mg / kg to about 10 mg / kg, about 0.01 mg / kg to about 5 mg / kg, about 0.5 mg / kg to about 5 mg / kg, about 1 mg / kg to about 5 mg / kg, about 5 mg / kg to about 15 mg / kg, about 5 mg / kg to 20 mg / kg, about 5 mg / kg to 25 mg / kg, about 5 mg / kg to 30 mg / kg, about 5 mg / kg to 35 mg / kg, about 5 mg / kg to 40 mg / kg, about 5 mg / kg to 50 mg / kg, about 10 mg / kg to 20 mg / kg, about 10 mg / kg to 30 mg / kg, about 10 mg / kg to 40 mg / kg, about 10 mg / kg to 50 mg / kg, about 20 mg / kg to 40 mg / kg, or about 20 mg / kg to 50 mg / kg body weight of the subject. In some examples, about 0.001 to 5 mg / kg of the HSP 90 inhibitor is administered. In some examples, about 0.001 to 10 mg / kg of the HSP 90 inhibitor is administered. Multiple doses of the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy can be administered to a subject, for example, the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy can be administered daily, every other day, twice per week, weekly, every other week, every three weeks, monthly, or less frequently. In some implementations, the HSP90 inhibitor and multikinase inhibitor are administered daily, every other day, twice per week, weekly, every other week, every three weeks, monthly for a period of time, for example, for two or more days, three or more days, 5 or more days, one week, two weeks, three weeks, four weeks, six weeks, twelve weeks, two months, three months, four months, five months, six months, a year, or longer. In some implementations, the GRP78 immunotherapy is administered to the subject at least twice, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10 times or more over a period of time, for example, one week, two weeks, three weeks, four weeks, six weeks, twelve weeks, two months, three months, four months, five months, six months, a year, or longer. In some implementations,7213-109906-02the HSP90 inhibitor and multikinase inhibitor are administered daily, every other day, or twice per week, and the GRP immunotherapy is administered twice, over a period of one month. In some implementations, treatment is a cycle of “on treatment” and “off treatment,” for example, the subject is “on treatment” (is administered the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy) for a period of time, such for one week, two weeks, three weeks, four weeks, six weeks, or longer, and is “off treatment” (not administered the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy) for a period of time, for example, for one week, two weeks, three weeks, four weeks, six weeks, or longer. In some implementations, the subject receives two or more cycles of treatment, for example, three, four, five, six, or more cycles of treatment. In some implementations, a higher “loading dose” is administered first and followed by subsequent “maintenance dose(s)” administered at a lower level. For example, an initial loading dose may be infused over a period of 30-120 minutes, followed by weekly maintenance doses for 4-8 weeks infused over 30-60 minute periods. The dosage and frequency of administration can be affected by a number of factors, for example, the condition being treated, severity of symptoms, the subject’s age or overall condition, etc. Typically, treatment regimens are determined by clinical trials. Any suitable route of administration can be used to administer the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy. Exemplary routes of administration include, but are not limited to, injection (for example, subcutaneous, intramuscular, intradermal, intraperitoneal, intratumoral, intraprostatic, intrathecal, intraarterial, intraosseous, and intravenous), oral, sublingual, rectal, transdermal, intranasal, vaginal and inhalation routes. In some examples, the HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy is administered parenterally, for example intravenously; however, injection or infusion in close proximity to a target tumor (e.g., local administration) or administration to the peritoneal cavity can also be used. In some implementations, the HSP90 inhibitor is administered intravenously or orally. In some implementations, the multikinase inhibitor is administered orally. In some implementations, the GRP78 immunotherapy is administered intravenously. The HSP90 inhibitor, multikinase inhibitor, and / or GRP78 immunotherapy can be administered by an osmotic pump (e.g., an Alzet pump) or mini-pump (e.g., an Alzet mini-osmotic pump), which allows for controlled, continuous and / or slow-release delivery of a therapeutic over a pre-determined period. The osmotic pump or mini-pump can be implanted subcutaneously, or near a target site. Appropriate routes of administration can be determined by a practitioner based on factors for example, the condition being treated, severity of symptoms, the subject’s age or overall condition, or other factors. The methods disclosed herein are useful to treat cancer. Exemplary cancers include sarcomas, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, and other sarcomas, synovioma, mesothelioma, Ewing's tumor, Kaposi sarcoma, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, lymphoid malignancy, pancreatic cancer, breast cancer, lung cancers, ovarian cancer, uterine cancer, prostate cancer, hepatocellular carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, adrenal carcinoma, sweat gland carcinoma, medullary thyroid carcinoma, papillary thyroid7213-109906-02carcinoma, pheochromocytomas sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, Wilms' tumor, cervical cancer, testicular tumor, seminoma, bladder carcinoma, melanoma, and CNS tumors (for example, a glioma (for example, brainstem glioma and mixed gliomas), glioblastoma (also known as glioblastoma multiforme) astrocytoma, CNS lymphoma, germinoma, medulloblastoma, Schwannoma craniopharyogioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, head and neck cancers, neuroblastoma, retinoblastoma and brain metastasis. Cancer also includes hematological (or hematogenous) cancers, for example, leukemia, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma (indolent or high grade forms), multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, myelodysplastic syndrome, hairy cell leukemia or myelodysplasia. In some implementations, the method is a method of treating lung, liver, breast, or pancreatic cancer. In some examples, the subject has lung, liver, breast, or pancreatic cancer. In some implementations, the subject has a cancer that expresses GRP78. In some examples, the cancer that expresses GRP78 is lung, liver, breast, or pancreatic cancer. In some implementations, a subject having a cancer that expresses or over-expresses GRP78 (e.g., relative to a non-cancerous cell of the same type) is selected for treatment. In some implementations, the cancer is not a hematological cancer or liquid tumor. In some implementations, the subject is further administered one or more cytokine(s) (for example, one or more of IL-2, IL-7, IL-15, IL-21, and / or IL-12), for example, to support survival and / or growth of the GRP78 immunotherapy, or specifically, the GRP78 NK-CAR cells disclosed herein. The cytokine(s) can be administered before, after, or substantially simultaneously with the GRP78 immunotherapy or GRP78 NK- CAR cells. In some examples, about 1 to about 5 cytokines are administered to the subject, for example, about 1 to about 4, about 1 to about 3, about 1 to about 2, about 2 to about 5, about 2 to about 4, about 2 to about 3, about 3 to about 5, about 3 to about 4, or about 4 to about 5 cytokines are administered, before, after, or substantially simultaneously with the GRP78 immunotherapy. In some examples, at least one of IL- 2, IL-7, or IL-15 is administered to the subject before, after, or substantially simultaneously with the GRP78 immunotherapy. In some examples, at least one cytokine (e.g., IL-2, IL-7, and / or IL-15) is administered simultaneously, for example, with GRP78 immunotherapy. In some implementations, the subject receives an additional treatment, for example, one or more of surgery, radiation, chemotherapy, immunotherapy (e.g., checkpoint inhibitor), or other therapeutic. Exemplary chemotherapeutic agents include (but are not limited to) alkylating agents, for example, nitrogen mustards (e.g., mechlorethamine, cyclophosphamide, melphalan, uracil mustard or chlorambucil), alkyl sulfonates (e.g., busulfan), nitrosoureas (e.g., carmustine, lomustine, semustine, streptozocin, or dacarbazine); antimetabolites, e.g., folic acid analogs (e.g., methotrexate), pyrimidine analogs (e.g., 5-FU or cytarabine), and purine analogs, for example, mercaptopurine or thioguanine; or natural products, for example vinca alkaloids (e.g., vinblastine, vincristine, or vindesine), epipodophyllotoxins (e.g., etoposide or teniposide), antibiotics (e.g., dactinomycin, daunorubicin, doxorubicin, bleomycin, plicamycin, or7213-109906-02mitocycin C), and enzymes (e.g., L-asparaginase). Additional agents include platinum coordination complexes (e.g., cis-diamine-dichloroplatinum II, also known as cisplatin), substituted ureas (e.g., hydroxyurea), methyl hydrazine derivatives (e.g., procarbazine), and adrenocrotical suppressants (e.g., mitotane and aminoglutethimide); hormones and antagonists, for example, adrenocorticosteroids (e.g., prednisone), progestins (e.g., hydroxyprogesterone caproate, medroxyprogesterone acetate, and magestrol acetate), estrogens (e.g., diethylstilbestrol and ethinyl estradiol), antiestrogens (e.g., tamoxifen), and androgens (e.g., testosterone proprionate and fluoxymesterone). Examples of the most commonly used chemotherapy drugs include adriamycin, melphalan (Alkeran®) Ara-C (cytarabine), carmustine, busulfan, lomustine, carboplatinum, cisplatinum, cyclophosphamide (Cytoxan®), daunorubicin, dacarbazine, 5- fluorouracil, fludarabine, hydroxyurea, idarubicin, ifosfamide, methotrexate, mithramycin, mitomycin, mitoxantrone, nitrogen mustard, paclitaxel (or other taxanes, for example, docetaxel), vinblastine, vincristine, VP-16, while newer drugs include gemcitabine (Gemzar®), trastuzumab (Herceptin®), irinotecan (CPT-11), leustatin, navelbine, rituximab (Rituxan®) imatinib (STI-571), Topotecan (Hycamtin®), capecitabine, ibritumomab (Zevalin®), and calcitriol. A skilled clinician can select appropriate additional therapies (from those listed here or other current therapies) for the subject, depending on factors for example, the subject, the cancer being treated, treatment history, and other factors. In some examples, the subject is administered a checkpoint inhibitor. In some examples, the checkpoint inhibitor targets PD-1, PD-L1, CTLA-4, CDK4, and / or CDK6. Exemplary checkpoint inhibitors include ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, palbociclib, ribociclib, and abemaciclib. Multiple doses of the checkpoint inhibitor can be administered to a subject, for example, administered twice daily, once daily, every other day, twice per week, weekly, every other week, every three weeks, monthly, or less frequently. A skilled clinician can select an administration schedule based on the subject, the condition being treated, the previous treatment history, tumor load and type, clinical stage and grade of the disease and overall health of the subject, or other factors. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting. Clauses Clause 1. A method of treating cancer in a subject, comprising administering to the subject an effective amount of: a HSP90 inhibitor, a multikinase inhibitor, and a GRP78 immunotherapy; thereby treating the cancer. Clause 2. The method of clause 1, wherein the GRP78 immunotherapy comprises adoptive cell therapy. Clause 3. The method of clause 1 or 2, wherein the adoptive cell therapy comprises a non-naturally occurring tumor infiltrating lymphocyte (TIL), engineered T cell receptor (TCR), or chimeric antigen receptor (CAR), and wherein the adoptive cell therapy specifically targets GRP78.7213-109906-02Clause 4. The method of any one of clauses 1-3, wherein the adoptive cell therapy comprises the CAR, and the CAR comprises a sequence having at least 90% sequence identity to SEQ ID NO: 1, or the CAR comprises SEQ ID NO: 1. Clause 5. The method of any one of clauses 1-4, wherein: (a) the CAR comprises a sequence having at least 90% sequence identity to SEQ ID NO: 8, or (b) the CAR comprises or consists of SEQ ID NO: 8. Clause 6. The method of any one of clauses 1-5, wherein the CAR is expressed in a NK cell, a T cell, or a NKT cell. Clause 7. The method of any one of clauses 1-6, wherein the CAR is expressed in a NK cell. Clause 8. The method of any one of clauses 1-7, wherein the HSP90 inhibitor comprises STA-9090, BIIB021, 17-AAG, or SNX-2112. Clause 9. The method of any one of clauses 1-8, wherein the multikinase inhibitor comprises regorafenib, sorafenib, or lenvatinib. Clause 10. The method of any one of clauses 1-9, wherein the HSP90 inhibitor comprises STA- 9090 and the multikinase inhibitor comprises regorafenib. Clause 11. The method of any one of clauses 1-10, wherein the GRP78 immunotherapy comprises a chimeric antigen receptor (CAR) that specifically binds GRP78. Clause 12. The method of any one of clauses 1-11, wherein the cancer comprises a solid tumor. Clause 13. The method of any one of clauses 1-12, wherein the cancer comprises lung, liver, breast, or pancreatic cancer. Clause 14. The method of any one of clauses 1-13, further comprising selecting a subject having a cancer that expresses cell surface GRP78 for treatment. Clause 15. The method of any one of clauses 1-14, wherein the HSP90 inhibitor and the multikinase inhibitor are administered to the subject first, followed by the GRP78 immunotherapy. Clause 16. The method of any one of clauses 1-15, further comprising: (a) detecting cell surface GRP78 expression on cancer cells of the subject; (b) administering the HSP90 inhibitor and the multikinase inhibitor; and (c) administering the GRP78 immunotherapy; optionally wherein an increase of cell surface GRP78 expression is detected after administering the HSP90 inhibitor and the multikinase inhibitor relative to step (a). Clause 17. A nucleic acid encoding a chimeric antigen receptor (CAR) expression cassette comprising: (i) a GRP78 CAR and (ii) an IL-15 domain. Clause 18. The nucleic acid of clause 17, wherein: (a) the GRP78 CAR comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1, or (b) the GRP78 CAR comprises SEQ ID NO: 1. Clause 19. The nucleic acid of clause 17 or 18, wherein: (a) the GRP78 CAR comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8, or (b) the GRP78 CAR comprises or consists of SEQ ID NO: 8.7213-109906-02Clause 20. The nucleic acid of any one of clauses 17-19, wherein: (a) the GRP78 CAR is encoded by a nucleic acid sequence comprising a sequence having at least 90% sequence identity to SEQ ID NO: 16, or (b) the GRP78 CAR is encoded by a nucleic acid sequence comprising or consisting of SEQ ID NO: 16. Clause 21. The nucleic acid of any one of clauses 17-20, wherein: (a) the nucleic acid comprises a sequence having at least 90% sequence identity to SEQ ID NO: 17, or (b) the nucleic acid comprises or consists of SEQ ID NO: 17. Clause 22. The nucleic acid of any one of clauses 17-21, wherein: (a) the nucleic acid comprises a sequence having at least 90% sequence identity to SEQ ID NO: 18, or (b) the nucleic acid comprises or consists of SEQ ID NO: 18. Clause 23. A vector comprising the nucleic acid of any one of clauses 17-22. Clause 24. A host cell comprising the nucleic acid of any one of clauses 17-22 or the vector of clause 23. Clause 25. The host cell of clause 24, wherein the host cell is an immune cell. Clause 26. The host cell of clause 24 or 25, wherein the host cell is a T cell, a NK cell, or a NKT cell. Clause 26. A pharmaceutical composition, including the nucleic acid of any one of clauses 17-22, the vector of clause 23, or the host cell of any one of clauses 24-26, and a pharmaceutically acceptable carrier. Clause 27. A method of producing GRP78 CAR immune cells, comprising transforming a population of immune cells with the nucleic acid of any one of clauses 17-22, or the vector of clause 23. Clause 28. The method of clause 27, wherein the population of immune cells is a population of T cells, NK cells, or NKT cells. Clause 29. The method of clause 27 or 28, wherein the population of immune cells is a population of NK cells. EXAMPLES The following examples are provided to illustrate certain features and / or implementations. These examples should not be construed to limit the disclosure to the particular features or implementations described. Example 1 Materials and Methods Antibodies and Reagents APC anti-human CD3 antibody (clone OKT3, BioLegend), FITC and PE / Cy7 anti-human CD56 antibody (clone HCD56, BioLegend), PE / Cy7 anti-human MICA / B (Clone 6D4, BioLegend), FITC anti- human CD3 antibody (clone UCHT1, BD Biosciences) were purchased from BD Biosciences (San Jose, CA, USA). Unconjugated anti-GRP78 / BiP (Clone ET-21, Sigma) and secondary antibody APC anti-rabbit H+L7213-109906-02(ThermoFisher) were used in the GRP78 characterizations. Regorafenib (BAY 73-4506), romidepsin (FK228), cisplatin (NSC119875) and ganetespib (STA-9090) were purchased from Selleck Chemicals. Anti-VEGFR2 (clone D5B1, Cell Signaling), anti-pVEGFR2 (Clone 19A10, Cell Signaling), anti-Akt (9272S, Cell Signaling), anti-pMek1 / 2 (9121S, Cell Signaling), anti-S6 Kinase (Clone 2F9, Cell signaling) and β-Actin HRP Conjugated (Clone 13E5, Cell Signaling) were used for Western blot analysis and were purchased from Cell Signaling Technologies (Danver, MA, USA). Animal Studies Wild-type NOD-scid IL2Rgamma null (NSG) mice were purchased from Jackson Laboratory (Bar Harbor, ME). The light cycle for the mouse facilities was 12h on and 12h off. To generate a xenograft model both male and female mice were engrafted with tumors (2x106cells per mouse) at 8 weeks old. Tumor cells were suspended in 100µL of PBS Corning® Matrigel® Matrix and injected in the subcutaneous flank region of each mouse. Once tumors were palpable (40–50 mm3) the mice were split into two cohorts to begin treatment with either GRP78 CAR-NK or Naïve NK cells. Mice were injected intravenously (i.v.) through the tail-vein with 5x106NK or CAR-NK cells in 100µL of PBS. Animal weight and tumor burden were measured twice a week. Tumor size was measured by caliper and the greatest longitudinal diameter (length) and the greatest transverse diameter (width) were recorded. Tumor sizes based on caliper measurements were calculated by the modified ellipsoidal formula. Tumor size was calculated as follows: tumor size (mm3) = ½ (length × width2). When the tumor burden was >2000 mm3or the animal’s weight reduced >20%, mice were euthanized. Animal survival data were recorded simultaneously. Cell lines and Cultures HCO2 and Hu1545 cell lines were from Dr. Chen Liu’s Lab in the Department of Pathology at Yale School of Medicine. MDA-MB-231-RFP-Doxy-GRP78 cell line was from Dr. Athanasia Panopoulos’ Lab in the Department of Biology at University of Notre Dame, and was used as a control cell line for GRP78 low expression. 293T, SK-Hep1, Huh7 and BXPC3 cell lines were purchased from the American Type Culture Collection (ATCC) and cultured following ATCC protocols. 721.221.mIL21 cells were previously described (Yang et al., Mol Ther-Meth Clin D 18:428-445, 2020). 721.221.mIL21 cells were cultured in RPMI-1640 (Corning) supplemented with 10% (v / v) fetal bovine serum (FBS) and 100 U / mL Penicillin- Streptomycin (Corning) at 37 ℃ with 5% (v / v) CO2. For NK cell expansion, 721.221.mIL21 cells were irradiated at a dose of 10,000 Rad, washed with PBS, and then used as feeder cells for NK cell expansion. 293T was cultured in DMEM (Corning) supplemented with 10% (v / v) fetal bovine serum (FBS) and 100 U / mL penicillin-streptomycin (Corning) at 37 ℃ with 5% (v / v) CO2. Primary NK cell expansion PBMCs were isolated from buffy coats purchased from New York Blood Center using Lymphocyte Separation Medium (Corning). For PBNK cell expansion, 5 × 106PBMCs were cultured with7213-109906-021 x 107irradiated feeder cells in 35 mL RPMI-1640 media with 10% Fetal Bovine Serum (Corning), 2mM L-Glutamine (Corning), 100 U / ml Penicillin-Streptomycin (Corning), 200 U / ml IL-2 (PeproTech), and 10 ng / ml IL-15 (PeproTech) in G-Rex 6 Multi-well cell culture plates (Wilson Wolf). For G-Rex 100M series bioreactors, 5-6 × 107PBMCs were cultured with 1 x 108irradiated feeder cells in 300 ml RPMI-1640. Media were changed every 2-3 days. Total cell numbers were counted using AO / PI by an automated cell counter (Nexcelom, MA). To determine the percentage of NK cells, cells were stained for CD3-PE and CD56-APC, followed by flow cytometry analysis. Fold Expansion was calculated using the formula ([absolute cell number day x] / [absolute cell # day 0]). Plasmid construction and retrovirus production A codon-optimized DNA fragment for human expression was synthesized by GENEWIZ encoding the GRP78 / BiP-specific binding peptide from a prior study (Kim et al., Biochemistry-Us 45: 9434-9444, 2006). The sequence was cloned into the SFG retroviral vector backbone in-frame with the human IgG1 tag, CD28 transmembrane domain, intracellular domain CD28 plus 4-1BB, and the ζ chain of the human TCR / CD3 complex. To produce GRP78-CAR retrovirus, 293T cells were transfected with a combination of plasmids containing GRP78-CAR, RDF, and PegPam3. Two CAR constructs were designed to serve as a negative control for GRP78 CAR-NK killing. The GRP78 CARmut is designed to have a loss of function intracellular domain by converting all tyrosines to phenylalanines in the CD28 and ζ chain of the human TCR / CD3 complex. Additionally, the GRP78 CARmut has a TRAFΔ in the 41BB intracellular domain. The GRP78 CARΔ has a truncation at the intracellular domain CD28 plus 4-1BB, and the ζ chain of the human TCR / CD3 complex. Transduction of expanded NK cells with GRP78-CAR To produce GRP78-CAR Moloney murine leukemia retrovirus, 293T cells were transfected with a combination of plasmids containing GRP78-CAR in SFG backbone, RDF, and PegPam3, as previously described with a CD19 CAR-NK (Yang et al., Mol Ther-Meth Clin D 18:428-445, 2020). NK cells were harvested on day 7 of expansion and transduced with GRP78-CAR retrovirus in plates coated with RetroNection (Clontech). Two days later, cells were transferred to G-Rex 6 Multi-well cell culture plate and maintained in 35 ml complete RPMI-1640 media with 200 U / ml IL-2 (PeproTech) and 10 ng / ml IL-15 (PeproTech). Media were changed every 3-4 days and 2 × 107cells were kept in each well for continued culture at each time. Total cell numbers were counted using Trypan Blue by an automated cell counter (Nexcelom, MA). To determine the percentage of NK cells and expression of CAR, cells were stained for CD3, CD56, and anti-human IgG(H+L) F(ab’)2 fragment and analyzed by flow cytometry. Fold change of transduction was calculated using the formula [(% CD56+CD3- CAR+cell day x] / [(% CD56+CD3- CAR+cell day 0]).7213-109906-02Cytotoxicity Assay To perform cytotoxicity assays for cell viability, cells were seeded in triplicates onto a 96-flat bottom plate (Corning) in 200 μL of DMEM 10% (v / v) fetal bovine serum (FBS) and 100 U / mL penicillin- streptomycin (Corning) overnight at 37 ℃ with 5% (v / v) CO2. The drugs were added to media and cells were incubated with drugs for 48 hours or 72 hours. After the incubation with drugs, Cell Counting Kit-8 reagent was added to each well and the plate was incubated at 37℃ / 5% CO2for 2 hours then read at absorbance 460 nm. Values were normalized to vehicle following the formula ((raw read therapy / raw read vehicle) x100) to calculate % Cell Viability. PI / Annexin V Apoptosis Assay To determine the effect of combination chemotherapy on apoptosis of NK cells, cells were seeded 0.1x106cells per well into a 12 well flat-bottom plate (Corning) with the chemotherapy in complete RPMI- 1640 media with 200 U / ml IL-2 and 10 ng / ml IL-15. Using a PI FITC AnnexinV Apoptosis Detection kit (556547, BD Pharmingen), cells were stained after treatment. FACS analysis was performed on a LSRII or LSR Fortessa™ flow cytometer (BD) using heat-killed cells as a control for flow-gating. PMT voltages were adjusted, and compensation values were calculated before data collection. Data were acquired using FACSDiva™ software (BD) and analyzed using FlowJo™ software (BD). Incucyte® Time-Lapse Killing Assay To perform a time-lapse of cell death, Incucyte® live-cell imaging system was used. Target cells were seeded into 96-flat bottom plates (Corning) and were treated with chemotherapies for 72 hours in 200 μL of DMEM 10% FBS at 37 ℃ with 5% (v / v) CO2. CD56+ NK cells were expanded at a 10:1 target / effector ratio in HAMS-F12 with 10% FBS media with 1μL of Incucyte® Annexin V Red Reagent for apoptosis by Sartorius Group in 100 μL of media. The assay was performed for 5 hours recordings every 20 minutes and analyzed using Sartorius software. Imaging was analyzed using Incucyte® Live-Cell Analysis Systems software. Western Blot MKIR-HCC and hepatocyte control cells were seeded (0.150x106cells) in a 6-well plate (Corning) and incubated overnight in 200 μL of DMEM 10% FBS at 37 ℃ with 5% (v / v) CO2. Chemotherapy was then added and cells were incubated for 72 hours in media at 37 ℃ with 5% (v / v) CO2. Cells were harvested using cell lifter (Fisher) in cooled PBS. Cells were treated with Pierce RIPA cell lysis buffer (ThermoFisher) with 1x Halt™ Protease and Phosphatase Inhibitor Cocktails (ThermoFisher) with gentle vortexing every 5 minutes (for a total of 15 minutes) on ice. The cells were then spun down at maximum speed for 30 minutes in a tabletop centrifuge at 4℃. The supernatant was removed and 6x Loading Buffer (BioRad) with 1 / 10 (v / v) β-mercaptoethanol (Sigma) was added. 10 ug of total protein was loaded into mini-protean TGX Gels (BioRad) and transferred using the wet tank blotting system (BioRad). Transferred7213-109906-02membranes were incubated with primary antibodies for 1 hour to overnight according to the sensitivity of each antibody. Transferred membranes were then incubated with an HRP-linked secondary antibody for 1 hour. Protein bands were visualized using a chemiluminescence detection system (Thermo Scientific). Each membrane was stripped and re-probed for β-actin, which was used as an internal loading control. Flow Cytometry Analysis Cells were stained with primary antibodies in 1% FBS on ice for 60 minutes, secondary antibodies (if unconjugated) for 15 minutes on ice, washed with PBS, and analyzed on a FACS LSRII or an LSR Fortessa™ flow cytometer (BD). PMT voltages were adjusted, and compensation values were calculated before data collection. All cell lines exposed to chemotherapies were gated using LIVE / DEAD® Viability / Cytotoxicity Kit (Invitrogen). Data were acquired using FACSDiva™ software (BD) and analyzed using FlowJo™ software (BD).51Cr Release Assay To evaluate the cytotoxic activity of PBNK cell, a standard 4-h51Cr release assay was used. Briefly, target cells BXPC3, HCO2, SK-Hep1, MDA-MB-231(GRP78 low) were labeled with51Cr at 37 °C for 2 hours and then resuspended at 2 × 105cells / mL in RPMI1640 medium with 10% FBS. Then, 1 × 104target cells were incubated with serially diluted PBNK cells at 37 °C for 4 hours. After centrifugation, supernatants were collected and released51Cr was measured with a gamma counter (Wallac, Turku, Finland). Cytotoxicity (as a percentage) was calculated as follows: [(sample − spontaneous release) / (maximum release − spontaneous release)] × 100. SK-Hep1 MKIR-HCC Xenograft Tumor Mouse Model Tumor cells (e.g., 2x106SK-Hep1 cells) were engrafted subcutaneously into the flank region of NSG mice. Once palpable, the mice were treated daily via oral gavage with a HSP90 inhibitor (e.g., STA- 9090) at a low dose (e.g., 0.5 mg / kg) and a multikinase inhibitor (e.g., regorafenib) at 1mg / kg for 72 hours per cycle. After a recovery period (e.g., 24 hours), the mice were treated with GRP78 immunotherapy (e.g., GRP78 CAR-NK via tail vein injection) at a dose of 5x106cells per mouse per dose. This treatment timeline was repeated for three cycles. Outcomes, such as mouse weight, tumor metastasis, tumor volume, and mouse survival, were followed throughout treatment. SK-Hep1 Cells include a Firefly Luciferase cassette which is activated using D-luciferin (Biosynth Ltd, United Kingdom). Mice were imaged using IVIS® spectrum (imaging system) and ROI were measured for tumor size. Additionally, the tumor size was measured by a caliper and the greatest longitudinal diameter (length), and the greatest transverse diameter (width) were recorded. Tumor sizes based on caliper measurements were calculated by the modified ellipsoidal formula. The tumor size was calculated as follows: tumor size (mm3) = ½ (length × width2). When the tumor burden was >2000 mm3or the animal’s weight reduced >20%, mice were euthanized.7213-109906-02Statistical Analysis Data are represented as Mean (average) ± SEM. Statistical significance was determined using a one-tailed unpaired Student T-test, one-way ANOVA, where indicated. P-values < 0.05 were considered statistically significant. Example 2 HSP90 Inhibition Sensitizes Cancer Cells to Chemotherapeutic Stress To determine the efficacy of HSP90 inhibition for treating MKIR-HCC in vitro, cell viability was evaluated with HSP90 inhibitor monotherapy as well as a combination therapy (HSP90 inhibitor with a multikinase inhibitor). Pharmacological inhibition of HSP90 with ganetespib (STA-9090) was shown to decrease MKIR-HCC cell viability when used in combination with FDA approved multikinase inhibitors as compared to vehicle (FIG.1A). Cisplatin combined with an HSP90 inhibitor had minimal effects, and there was minimal toxicity to the hepatocyte control cell line Hu1545 (FIG.1B). This dependency is similar in several MKI-resistant Pancreatic Ductal Adenocarcinoma cell lines (Panc1, BXPC3 and MiaPaca2) when compared to the hepatocyte control cell line Hu1545 (FIG.1C). VEGFR2 is a target of multikinase inhibitor regorafenib, thus phosphorylation of VEGFR2 is reduced upon regorafenib treatment in drug-sensitive cells. In the MKIR-HCC cell line (which is MKI resistant) there was no reduction in pVEGFR2 after regorafenib monotherapy treatment, however, upon HSP90 inhibition there were reductions in VEGFR2 phosphorylation (FIGS.2A-2C). Additional signaling downstream of VEGFR2 was evaluated showing reductions upon combination therapy. Both HCC and PDAC cells are HSP90-dependent, therefore when HSP90 is pharmacologically inhibited the tumorigenic pathways are downregulated. These data indicate that HSP90 supports tumor cell survival under chemotherapeutic stress. HSP90 is a molecular chaperone that helps regulate the stability and function of many other proteins, including signaling proteins and transcription factors. How this translates to anti-tumor immunity remains unclear. MHC Class I chain-related protein A and B (MICA / B) is an important activating ligand for NK cells through binding to the NKG2D receptor on NK cells. It was found that combination chemotherapy (STA+Regor) recovers surface expression of MICA / B in MKIR-HCC cells as compared to regorafenib treatment alone, suggesting that HSP90 inhibition promotes recovery of surface MICA / B under chemotherapeutic pressure. (FIG.3A). While most CARs and chemotherapies have severe toxicities against healthy hematopoietic cells, the combination chemotherapy (STA+Regor) was found to have minimal effect on MICA / B activating ligand expression on hematopoietic cells (FIG.3B). Romidepsin, an HDAC inhibitor, was used as a positive control as it has been shown to induce MICA / B expression. These data demonstrate that HSP90 inhibition selectively improves MKIR-HCC sensitivity to chemotherapeutic stress and promotes recovery of NK-cell activating ligand MICA / B expression.7213-109906-02Example 3 HSP90 Inhibitors Stabilize NK-Cell Mediated Killing of Tumor Cells Many chemotherapies, such as methotrexate and protein tyrosine kinase inhibitors, are toxic to immune cells, reducing anti-tumor immunity. In the context of HSP90 inhibitors, high-dose HSP90 inhibition reduces MHC presentation, thus impeding T cell mediated killing of tumor cells. To determine whether HSP90 inhibition has any effects on NK cells, cell death of expanded NK cells after 48-hours of high dose monotherapies and combination chemotherapy was evaluated. Both BIIB021 and STA-9090 were tested, and no significant reductions in cell viability were observed (FIGS.5A-5B). To evaluate functionality of NK cells following combination chemotherapy treatment of MKIR- HCC, a killing assay using cell death marker Annexin-V was performed. Regorafenib monotherapy with NK cell treatment killed less than the combination chemotherapy with NK Cell groups (FIG.6). Combination chemotherapy (STA-9090 with regorafenib) showed baseline cell death with an increase upon the addition of NK cells (FIG.6). NK cells alone do not express phosphatidylserine, therefore minimal changes in Annexin-V staining were observed. These results show that the combination chemotherapy has minimal effects on expanded NK cell survival and function. Example 4 HSP90 Inhibitor-Enhanced Chemotherapy Increases GRP78 Expression on Solid Tumors Heat shock proteins can be overexpressed in tumor tissues and minimally expressed in non-tumor tissues, making them candidate immunotherapy targets. However, many do not have stable surface expression in solid tumors, such as MKIR-HCC. It was found that GRP78 had significantly higher expression across HCC and PDAC cell lines as compared to expanded CD3+T cells (FIGS.7A-7B). Engineered MDA-MB-231 (breast cancer), which contains doxycycline-inducible GRP78, was used as a negative control (absent doxycycline, MDA-MB-231 has low GRP78 expression). Variations in baseline GRP78 expression was observed in MKIR-HCC as compared to the negative control, with many having low GRP78 expression (although higher than CD3+expanded T- cells). Very little is known about the effect of HSP90 inhibition on the expression of surface HSPs. Strikingly, it was found that HSP90 inhibition, as well as the combination therapy with regorafenib, significantly increased expression of surface GRP78 in MKIR-HCC cells (FIG.8A). Treatment did not change GRP78 expression in the hepatocyte control cell line (FIG.8B). Surface GRP78 is conserved between mammals, thus to investigate the effect on GRP78 expression in vivo, wild-type NSG mice were treated with 3 cycles of combination chemotherapy (regorafenib (5mg / kg) and STA-9090 (0.5 mg / kg)) for 72-hours per cycle. Following treatment, GRP78 expression was significantly higher in tumor tissue than non-tumor tissue (FIG.9). Thus, the combination chemotherapy (HSP90 inhibitor + regorafenib) induces and stabilizes expression of cell surface GRP78 in MKIR-HCC cells. Stabilization of cell surface GRP78 provides an opportunity to increase the effectiveness of immunotherapies targeting GRP78, such as GRP78 CARs.7213-109906-02Example 5 GRP78 CAR-NK Cells Kill MKIR-HCC Cells In Vitro To target GRP78, a CAR using a peptide that specifically binds GRP78 was developed. The CAR construct included an IL-15 domain to promote the persistence of NK cells in vivo and an IgG1 domain (tag region) to detect the CAR using flow cytometry (FIG.10A). The construct was transduced into expanded NK cells and was stably expressed at 10 days (FIG.10B). To evaluate the viability and expansion of the GRP78-CAR-NK, it was compared to naïve untransduced expanded NK cells and CD19 CAR-NK cells. The GRP78-CAR-NK does not exhibit significant differences in cell viability up to 20 days post- transduction (FIG.11A). The expansion of GRP78 CAR-NK was found to be similar to other CAR constructs and naïve cells (FIG.11B). To evaluate transduction efficiency across CAR constructs, CD56+ CAR+ cell percent was measured. All CAR-NK constructs exhibited similar transduction efficiency when compared to naïve expanded NK Cells (FIG.12A). The transduction efficiency is stable for up to 15 days with minimal differences between the constructs (FIG.12B). To test killing efficacy, the GRP78 CAR-NK cells were incubated with various multikinase inhibitor (MKI)-resistant cell lines. BXPC3, SK-Hep1 and HCO2 cell lines had the highest killing difference when compared to naïve NK cells (FIGS.13A-13C). To validate chromium release data, Incucyte® (live-cell analysis system) imaging of SK-Hep1 cells incubated with either naïve or GRP78 CAR transduced NK cells for 24 hours was performed. AnnexinV was used as a readout of cell death. It was found that GRP78-IL15- CAR kills SK-Hep1 cells more than naïve expanded cells (FIG.14). The results demonstrate that the GRP78 CAR can be successfully transduced into 221mIL21 feeder cell expanded NK cells, and that the resulting GRP78 CAR-NK cells can target and kill GRP78-positive cancer cell lines in vitro. Example 6 GRP78-CAR-NK Cells Kill GRP78-Positive Tumors In Vivo Efficacy of the GRP78 CAR-NK cells was evaluated in vivo using a xenograft mouse model. A tumor engraftment of 2x106SK-Hep1 cells was administered subcutaneously into the flank region of NSG mice. Three doses of either naïve NK cells, or GRP78 CAR-NK, were administered, as shown in FIG.15. Mouse weight, tumor volume and survival were tracked until endpoint criteria were reached (FIGS.16A- 16C). While there was minimal control of tumor volume and mouse weight, there was a significant improvement in mouse survival as compared to naïve NK cell control. On day 60, mice died from metastasis and malignant ascites, suggesting that the CAR therapy provided temporary control without complete elimination of the tumor.7213-109906-02Example 7 GRP78-CAR-NK Cells and Combination Chemotherapy In addition to sensitizing cancer cells to environmental stress, the combination chemotherapy appears to increase and stabilize cell surface GRP78 and NK activating ligand MICA / B, thereby potentially promoting GRP78 CAR-NK mediated cancer cell killing. Thus, it was hypothesized that combining GRP78 CAR-NK immunotherapy with combination chemotherapy (a HSP90 inhibitor and multikinase inhibitor) would improve effectiveness of treatment. Tumor cells (2x106SK-Hep1 cells were engrafted subcutaneously into the flank region of NSG mice. Once palpable, the mice were treated once daily for three consecutive days via oral gavage with a HSP90 inhibitor (STA-9090) at a low dose (0.5 mg / kg) and a multikinase inhibitor (regorafenib) at 1 mg / kg. After a recovery period (24 hours), the mice were treated with GRP78 immunotherapy (5x106GRP78 CAR- NK cells per mouse via tail vein injection). This treatment timeline was repeated for three cycles (FIG. 17A). Mice that received GRP78 CAR-NK treatment exhibited a significant improvement in survival. Mice that received both GRP78 CAR-NK and chemotherapy had a trending improvement in survival and lived the longest (FIG.17B). A significant suppression of tumor growth was also observed in the immunotherapy-chemotherapy combination treatment relative to any of the other treatment groups (FIG. 17C). The immunotherapy-chemotherapy combination group also had fewer liver metastasis (harvested after day 5) relative to other groups (FIG.17D). In addition, it was found that tumors treated with the GRP78 immunotherapy or the immunotherapy-chemotherapy combination therapy showed significant reductions in tumor weight (FIG.17E). To further validate the efficacy of GRP78 immunotherapy combined with HSP90i-MKI adjuvant chemotherapy, mice were imaged after ending treatments on day 23, 30, 44 and 51. It was found that tumor growth and metastasis was suppressed in GRP78 CAR-NK treated groups as compared to chemotherapy- only or vehicle groups (FIGS.18A-18C). To evaluate safety and efficacy, mouse weight was measured biweekly during the study. Vehicle group mice were found to drop in weight earlier than the GRP78 CAR-NK treated mice (FIGS.19A-19B). Mice in all groups were found to have progression of tumor growth and metastasis after day 20 of treatment, suggesting that therapy suppresses tumor growth rather than completely eliminating the tumor. However, the GRP78 immunotherapy combined with HSP90i-MKI adjuvant chemotherapy achieved the most suppression of tumor growth (FIGS.19C-19D). It is typical for CAR therapies in the NSG mouse model to exhibit suppression of solid tumor growth rather than eradication. This is due at least in part to the nature of the NSG model, which lacks a functional immune system capable of promoting the complete eradication of tumors. Metastatic tumor models are very aggressive and show short survival. In fact, the inventors are not aware of any treatments that have shown complete eradication of tumors using the model described in this example. Thus, further suppressing tumor growth and extending mouse survival, as shown herein, is a significant result.7213-109906-02Surface Heat Shock Proteins are a controversial target for immunotherapy. In their surface form, they have been described as having both immunosuppressive and immunostimulatory roles. The mechanisms underlying these seemingly contradictory effects are poorly understood. Surface heat shock proteins such as GRP78 have also been shown to be tumorigenic, although data disclosed in this application does not seem to indicate that GRP78 is tumorigenic. While some have pursued targeting heat shock response for the treatment of cancer, traditional approaches have failed to realize clinical efficacy. HSP90 inhibitors as a monotherapy are ineffective, toxic, and are linked to immunosuppression. In addition, CAR therapy has shown minimal efficacy for treating solid tumors. Surprisingly, here it is shown that precise rebalancing of the heat shock response using a low-dose HSP90 inhibitor promotes the stable presentation of surface GRP78, thereby providing a strong and selective target for immunotherapy while also avoiding the pitfalls of traditional HSP90 monotherapy. Although a specific example is provided herein, a practitioner could use a similar procedure to test different tumor cells, different HSP90 inhibitors (e.g., STA-9090, BIIB021, 17-AAG, or SNX-2112), different multikinase inhibitors (e.g., regorafenib, sorafenib, or lenvatinib), and / or GRP78 immunotherapies. In addition, similar procedures could be used to test or optimize dosages, for example, of the GRP78 immunotherapy, HSP90 inhibitor, or MKI. It will be apparent that the precise details of the methods or compositions described may be varied or modified without departing from the spirit of the described aspects of the disclosure. We claim all such modifications and variations that fall within the scope and spirit of the claims below.

Claims

7213-109906-02We claim:

1. A method of treating cancer in a subject, comprising administering to the subject an effective amount of: a HSP90 inhibitor, a multikinase inhibitor, and a GRP78 immunotherapy; thereby treating the cancer.

2. The method of claim 1, wherein the GRP78 immunotherapy comprises adoptive cell therapy.

3. The method of claim 2, wherein the adoptive cell therapy comprises a non-naturally occurring tumor infiltrating lymphocyte (TIL), engineered T cell receptor (TCR), or chimeric antigen receptor (CAR), and wherein the adoptive cell therapy specifically targets GRP78.

4. The method of claim 3, wherein the adoptive cell therapy comprises the CAR, and the CAR comprises a sequence having at least 90% sequence identity to SEQ ID NO: 1, or the CAR comprises SEQ ID NO:

1.

5. The method of claim 4, wherein: (a) the CAR comprises a sequence having at least 90% sequence identity to SEQ ID NO: 8, or (b) the CAR comprises or consists of SEQ ID NO:

8.

6. The method of claim 1, further comprising selecting a subject having a cancer that expresses cell surface GRP78 for treatment.

7. The method of claim 3, wherein the CAR is expressed in a NK cell, a T cell, or a NKT cell.

8. The method of claim 7, wherein the CAR is expressed in a NK cell.

9. The method of claim 1, wherein: i) the HSP90 inhibitor comprises STA-9090, BIIB021, 17-AAG, or SNX-2112, and / or ii) the multikinase inhibitor comprises regorafenib, sorafenib, or lenvatinib.

10. The method of claim 1, wherein the HSP90 inhibitor comprises STA-9090 and the multikinase inhibitor comprises regorafenib.7213-109906-0211. The method of claim 10, wherein the GRP78 immunotherapy comprises a chimeric antigen receptor (CAR) that specifically binds GRP78.

12. The method of claim 1, wherein the HSP90 inhibitor and the multikinase inhibitor are administered to the subject prior to the GRP78 immunotherapy.

13. The method of claim 1, wherein the cancer comprises a solid tumor.

14. The method of claim 1, wherein the cancer comprises lung, liver, breast, or pancreatic cancer.

15. The method of claim 1, further comprising: (a) detecting cell surface GRP78 expression on cancer cells of the subject; (b) administering the HSP90 inhibitor and the multikinase inhibitor to stabilize GRP78 expression; (c) detecting an increase of cell surface GRP78 expression relative to step (a); and (d) administering the GRP78 immunotherapy; thereby treating the cancer.

16. A nucleic acid encoding a chimeric antigen receptor (CAR) expression cassette comprising: (i) a GRP78 CAR; and (ii) an IL-15 domain.

17. The nucleic acid of claim 16, wherein: (a) the GRP78 CAR comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1; or (b) the GRP78 CAR comprises SEQ ID NO:

1.

18. The nucleic acid of claim 16, wherein: (a) the GRP78 CAR comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8, or (b) the GRP78 CAR comprises or consists of SEQ ID NO:

8.

19. The nucleic acid of claim 16, wherein: (a) the GRP78 CAR is encoded by a nucleic acid sequence comprising a sequence having at least 90% sequence identity to SEQ ID NO: 16, or (b) the GRP78 CAR is encoded by a nucleic acid sequence comprising or consisting of SEQ ID NO: 16.7213-109906-0220. The nucleic acid of claim 16, wherein: (a) the nucleic acid comprises a sequence having at least 90% sequence identity to SEQ ID NO: 17, or (b) the nucleic acid comprises or consists of SEQ ID NO:

17.

21. The nucleic acid of claim 16, wherein: (a) the nucleic acid comprises a sequence having at least 90% sequence identity to SEQ ID NO: 18, or (b) the nucleic acid comprises or consists of SEQ ID NO:

18.

22. A vector comprising the nucleic acid of claim 16.

23. A host cell comprising the nucleic acid of claim 16 or a vector encoding the nucleic acid.

24. The host cell of claim 23, wherein the host cell is an immune cell.

25. The host cell of claim 24, wherein the immune cell is a T cell, a NK cell, or a NKT cell.

26. A pharmaceutical composition, comprising the nucleic acid of claim 16 and a pharmaceutically acceptable carrier.

27. The pharmaceutical composition of claim 26, wherein the nucleic acid is comprised in a vector or host cell.

28. A method of producing GRP78 CAR immune cells, comprising transforming a population of immune cells with the nucleic acid of claim 16 or a vector encoding the nucleic acid.

29. The method of claim 28, wherein the population of immune cells is a population of T cells, NK cells, or NKT cells.

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