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US 2021/0330783 A1Published application
Hiv pre-immunization and immunotherapy
AssigneeAmerican Gene Technologies International Inc.
InventorsCharles David Pauza, Haishan Li, Tyler Lahusen, Jeff Galvin
Life of this patent
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Abstract
The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.
Claims94
A lentiviral vector comprising at least one encoded genetic element, wherein the at least one encoded genetic element comprises
- each of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2 and (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- two of:
- (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7.
7 more elements
The lentiviral vector of claim 2, wherein the at least one encoded genetic element comprises:
- each of:
- SEQ ID NO:
- 2 and SEQ ID NO:
- 108 or
- two of:
- SEQ ID NO:
- 97, SEQ ID NO:
- 6, and SEQ ID NO:
- 7.
6 more elements
A method of treating cells infected with HIV, the method comprising:
- (a) obtaining, or having obtained, peripheral blood mononuclear cells (PBMC) from a subject infected with HIV, wherein the subject has been previously immunized with a therapeutically effective amount of a first stimulatory agent;
- (b) contacting, or having contacted, the PBMC with a therapeutically effective amount of a second stimulatory agent, wherein the contacting is carried out ex vivo;
- (c) transducing, or having transduced, the PBMC ex vivo with a viral delivery system encoding at least one genetic element, wherein at least one encoded genetic element comprises:
- each of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2 and (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- two of:
- (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7;
- and
- (d) culturing, or having cultured, the transduced PBMC for at least 1 day.
12 more elements
A method of treating HIV infection in a subject, the method comprising:
- (a) removing, or having removed, leukocytes from the subject, wherein the subject has been previously immunized with a therapeutically effective amount of a first stimulatory agent;
- (b) purifying, or having purified, peripheral blood mononuclear cells (PBMC) ex vivo from the leukocytes;
- (c) contacting, or having contacted, the PBMC ex vivo with a therapeutically effective amount of a second stimulatory agent;
- (d) transducing, of having transduced, the PBMC ex vivo with a viral delivery system encoding at least one genetic element, wherein the at least one genetic element comprises:
- each of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2 and (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- two of:
- (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7;
- and
- (e) culturing, or having cultured, the transduced PBMC for at least 1 day.
13 more elements
A lentiviral vector comprising an encoded microRNA cluster, wherein the encoded microRNA cluster comprises a sequence comprising (i) at least 90% sequence identity with SEQ ID NO:
- 1, (ii) at least 90% sequence identity with SEQ ID NO:
- 2, and (iii) at least 90% sequence identity with SEQ ID NO:
- 108.
A lentiviral particle capable of infecting a target cell, the lentiviral particle comprising:
- (a) an envelope protein capable of infecting the target cell;
- and
- (b) an encoded microRNA cluster, wherein the encoded microRNA cluster comprises a sequence comprising (i) at least 90% sequence identity with SEQ ID NO:
- 1, (ii) at least 90% sequence identity with SEQ ID NO:
- 2, and (iii) at least 90% sequence identity with SEQ ID NO:
- 108.
3 more elements
A modified cell comprising a primary T cell infected with a lentiviral particle, wherein the lentiviral particle comprises:
- (a) an envelope protein capable of infecting the target cell;
- and
- (b) an encoded microRNA cluster, wherein the encoded microRNA cluster comprises a sequence comprising (i) at least 90% sequence identity with SEQ ID NO:
- 1, (ii) at least 90% sequence identity with SEQ ID NO:
- 2, and (iii) at least 90% sequence identity with SEQ ID NO:
- 108.
3 more elements
A method of treating cells infected with HIV, the method comprising:
- (a) contacting or having contacted peripheral blood mononuclear cells (PBMC) isolated from a subject infected with HIV with a therapeutically effective amount of an ex vivo stimulatory agent, wherein the contacting is conducted ex vivo;
- (b) transducing or having transduced the PBMC ex vivo with a lentiviral particle, wherein the lentiviral particle comprises:
- (i) an envelope protein capable of infecting the PBMC;
- and
- (ii) an encoded microRNA cluster, wherein the encoded microRNA cluster comprises a sequence comprising (a) at least 90% sequence identity with SEQ ID NO:
- 1, (b) at least 90% sequence identity with SEQ ID NO:
- 2, and (c) at least 90% sequence identity with SEQ ID NO:
- 108.
5 more elements
A lentiviral vector comprising at least one encoded genetic element, wherein the at least one encoded genetic element comprises
- at least two of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 1, (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2, and (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- each of:
- (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (vi) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7.
8 more elements
A method of treating cells infected with HIV, the method comprising:
- (a) obtaining, or having obtained, peripheral blood mononuclear cells (PBMC) from a subject infected with HIV, wherein the subject has been previously immunized with a therapeutically effective amount of a first stimulatory agent;
- (b) contacting, or having contacted, the PBMC with a therapeutically effective amount of a second stimulatory agent, wherein the contacting is carried out ex vivo;
- (c) transducing, or having transduced, the PBMC ex vivo with a viral delivery system encoding at least one genetic element, wherein at least one encoded genetic element comprises:
- at least two of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 1, (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2, and (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- each of:
- (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (vi) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7;
- and
- (d) culturing, or having cultured, the transduced PBMC for at least 1 day.
13 more elements
A method of treating HIV infection in a subject, the method comprising:
- (a) removing, or having removed, leukocytes from the subject, wherein the subject has been previously immunized with a therapeutically effective amount of a first stimulatory agent;
- (b) purifying, or having purified, peripheral blood mononuclear cells (PBMC) ex vivo from the leukocytes;
- (c) contacting, or having contacted, the PBMC ex vivo with a therapeutically effective amount of a second stimulatory agent;
- (d) transducing, of having transduced, the PBMC ex vivo with a viral delivery system encoding at least one genetic element, wherein the at least one genetic element comprises:
- at least two of:
- (i) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 1, (ii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 2, and (iii) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 108;
- or
- each of:
- (iv) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 97, (v) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 6, and (vi) a sequence comprising at least 80% sequence identity with SEQ ID NO:
- 7;
- and
- (e) culturing, or having cultured, the transduced PBMC for at least 1 day.
14 more elements
Dependencies are inferred from the claim text.