Exhibit 4.2

AMENDMENT AND WAIVER

OF

FOURTH AMENDED AND RESTATED

INVESTORS’ RIGHTS AGREEMENT

OF JUNO THERAPEUTICS, INC.

July 27, 2015

This Amendment and Waiver dated as of July 27, 2015 (the “Amendment and Waiver”) amends and waives certain provisions of that certain Fourth Amended and Restated Investors’ Rights Agreement dated as of December 5, 2014 (the “Agreement”), between Juno Therapeutics, Inc., a Delaware corporation (the “Company”), and the Investors named therein. Capitalized terms used herein without definition shall have the meanings given in the Agreement.

RECITALS

A. The Agreement provides, among other things, for certain registration rights granted by the Company to the Investors.

B. One June 29, 2015, the Company entered into a Registration Rights Agreement (the “Celgene Agreement”) with Celgene Corporation and Celgene RIVOT Ltd (together, “Celgene”) granting certain registration rights to Celgene.

C. The Celgene Agreement provides that the registration rights granted to Celgene are subject to the prior, senior right of the Investors under the Agreement until such time as the Company obtains a waiver from the Investors under the Agreement.

D. Under Section 6.1 of the Agreement, the Company and the holders of at least a majority of the Registrable Securities issued upon conversion of the Company’s preferred stock, voting together as a single class, may amend or waive any term of the Agreement.

E. The Company and the Investors party hereto desire to amend and waive the Agreement to allow Celgene to exercise its registration rights under the Celgene Agreement without being subject to the rights of the Investors under the Agreement.

AMENDMENT AND WAIVER

For good and valuable consideration, the receipt and adequacy of which are hereby acknowledged, the Investors party hereto, voting together as a single class in accordance with Section 6.1 of the Agreement, hereby amend and waive the Agreement on behalf of all Investors thereunder as follows:

1. The registration rights granted to Celgene under the Celgene Agreement shall not be subject to the rights of the Investors under Section 2.2 of the Agreement, except that Celgene’s rights under Section 6(f) of the Celgene Agreement shall remain subject to the rights of the Investors under the Agreement such that Celgene’s exercise of its rights under Section 6(f) of the Celgene Agreement shall not reduce the amount of securities to be registered on the associated registration statement by the Investors pursuant to registration rights provided under the Agreement.

2. Without limiting the generality of the foregoing, Celgene and its permitted transferees and assigns may exercise its registration rights under the Celgene Agreement (other than those in Section 6(f) of the Celgene Agreement) without being subject to the notice or inclusion requirements under Section 2.2(a) of the Agreement or the underwriters’ cutback provision under Section 2.2(b) of the Agreement.

3. The application of Section 2.12 of the Agreement is hereby waived with respect to the Celgene Agreement and the rights granted thereunder.

4. Nothing herein shall derogate from any rights of the Investors under the Agreement, including without limitation their right to request registration of their Registrable Securities under the Agreement, except to the extent set forth in the limited amendment and waiver above. The Agreement as amended hereby shall continue in full force and effect from and after the date hereof.

(signature page follows)

The parties are signing this Amendment and Waiver as of the date stated in the introductory clause.

(Signature page to the Amendment and Waiver)

The parties are signing this Amendment and Waiver as of the date stated in the introductory clause.

(Signature page to the Amendment and Waiver)

The parties are signing this Amendment and Waiver as of the date stated in the introductory clause.

(Signature page to the Amendment and Waiver)